SLIT2 - Revision history

Dmitry Dzhagarov at 10:45, 21 September 2024

2024-09-21T10:45:07Z

← Older revision		Revision as of 10:45, 21 September 2024
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	<ref>Jones, C. A., Nishiya, N., London, N. R., Zhu, W., Sorensen, L. K., Chan, A. C., ... & Li, D. Y. (2009). Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology, 11(11), 1325-1331. PMID: 19855388 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854659/ PMC2854659] DOI: 10.1038/ncb1976</ref>		<ref>Jones, C. A., Nishiya, N., London, N. R., Zhu, W., Sorensen, L. K., Chan, A. C., ... & Li, D. Y. (2009). Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology, 11(11), 1325-1331. PMID: 19855388 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854659/ PMC2854659] DOI: 10.1038/ncb1976</ref>

	During infection, Mycobacterium tuberculosis (Mtb) rewires distinct host signaling pathways that results in pathogen-favorable outcomes. In particular induced expression of the neuronal ligand SLIT2 which was due to the Mtb-mediated phosphorylation of the P38/JNK pathways. Activation of these kinases resulted in the loss of the repressive H3K27me3 signature on the Slit2 promoter.<ref>Borbora, S. M., Satish, B. A., Sundar, S., Bhatt, S., & Balaji, K. N. (2023). Mycobacterium tuberculosis elevates SLIT2 expression within the host and contributes to oxidative stress responses during infection. The Journal of Infectious Diseases, jiad126. PMID: 37158474 [https://doi.org/10.1093/infdis/jiad126 DOI: 10.1093/infdis/jiad126</ref> I noticed that many centenarians came from families where the incidence of tuberculosis was high (for example Jeanne Calment). This allows me to assume as a working hypothesis that perhaps activation of the Slit2 gene by Mtb is involved in their longevity.		During infection, Mycobacterium tuberculosis (Mtb) rewires distinct host signaling pathways that results in pathogen-favorable outcomes. In particular induced expression of the neuronal ligand SLIT2 which was due to the Mtb-mediated phosphorylation of the P38/[[Role of JNK in aging\|JNK]] pathways. Activation of these kinases resulted in the loss of the repressive H3K27me3 signature on the Slit2 promoter.<ref>Borbora, S. M., Satish, B. A., Sundar, S., Bhatt, S., & Balaji, K. N. (2023). Mycobacterium tuberculosis elevates SLIT2 expression within the host and contributes to oxidative stress responses during infection. The Journal of Infectious Diseases, jiad126. PMID: 37158474 [https://doi.org/10.1093/infdis/jiad126 DOI: 10.1093/infdis/jiad126</ref> I noticed that many centenarians came from families where the incidence of tuberculosis was high (for example Jeanne Calment). This allows me to assume as a working hypothesis that perhaps activation of the Slit2 gene by Mtb is involved in their longevity.

	== References ==		== References ==

Dmitry Dzhagarov at 17:12, 25 November 2023

2023-11-25T17:12:11Z

← Older revision		Revision as of 17:12, 25 November 2023
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	<ref>Li, Q., Huang, L., Ding, Y., Sherchan, P., Peng, W., & Zhang, J. H. (2023). Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1–srGAP1 pathway in a rat model of germinal matrix hemorrhage. Journal of Neuroinflammation, 20(1), 249. PMID: 37899442 PMCID: PMC10613398 DOI: 10.1186/s12974-023-02935-2</ref>		<ref>Li, Q., Huang, L., Ding, Y., Sherchan, P., Peng, W., & Zhang, J. H. (2023). Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1–srGAP1 pathway in a rat model of germinal matrix hemorrhage. Journal of Neuroinflammation, 20(1), 249. PMID: 37899442 PMCID: PMC10613398 DOI: 10.1186/s12974-023-02935-2</ref>
	<ref>Li, X., Zheng, S., Tan, W., Chen, H., Li, X., Wu, J., ... & Yang, F. H. (2020). Slit2 protects hearts against ischemia-reperfusion injury by inhibiting inflammatory responses and maintaining myofilament contractile properties. Frontiers in physiology, 11, 228. PMID: 32292352 PMCID: PMC7135862 DOI: 10.3389/fphys.2020.00228</ref>		<ref>Li, X., Zheng, S., Tan, W., Chen, H., Li, X., Wu, J., ... & Yang, F. H. (2020). Slit2 protects hearts against ischemia-reperfusion injury by inhibiting inflammatory responses and maintaining myofilament contractile properties. Frontiers in physiology, 11, 228. PMID: 32292352 PMCID: PMC7135862 DOI: 10.3389/fphys.2020.00228</ref>
	<ref>Kim, Y. H., Lee, Y. K., Park, S. S., Park, S. H., Eom, S. Y., Lee, Y. S., ... & Park, T. J. (2023). Mid-old cells are a potential target for anti-aging interventions in the elderly. Nature Communications, 14(1), 7619. [https://doi.org/10.1038/s41467-023-43491-w DOI: 10.1038/s41467-023-43491-w]</ref>
			SLIT2 progressively decreases as cells become senescent.<ref name="Mid-old" >Kim, Y. H., Lee, Y. K., Park, S. S., Park, S. H., Eom, S. Y., Lee, Y. S., ... & Park, T. J. (2023). Mid-old cells are a potential target for anti-aging interventions in the elderly. Nature Communications, 14(1), 7619. [https://doi.org/10.1038/s41467-023-43491-w DOI: 10.1038/s41467-023-43491-w]</ref> Treatment with '''recombinant human SLIT2 protein (rhSLIT2)''' resulted in decreased expression of inflammatory genes and proteins. In particular long-term treatment with rhSLIT2 protein resulted in upregulated expression of SOX2 and OCT4 and restored the morphology of mid-old (but not in old) fibroblasts, causing them to revert to a small and spindle-shaped morphology reminiscent of young cells. The proliferative capacity of such mid-old fibroblasts was recovered, accompanied by decreased levels of p21<sup>Waf1</sup> mRNA and protein in a [[P53 protein involvement in Longevity\|p53]]-independent manner.<ref name="Mid-old" />

			In the animal experiments with 23-month-old male mice treated by rmSLIT2 10 times over a duration of several weeks, mouse aging-related characteristics significantly improved. Specifically, activity in the cage and hanging ability increased. However, blood analysis showed no significant difference between the control and rmSLIT2-treated groups.<ref name="Mid-old" />
			Surprisingly, SLIT2 decreased inflammatory response and improved proliferative capacity only in mid-old, but not in old fibroblasts.<ref name="Mid-old" />

	<ref>Zhao, H., Anand, A. R., & Ganju, R. K. (2014). Slit2–Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia. The Journal of Immunology, 192(1), 385-393. PMID: 24272999 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908786/ PMC3908786] DOI: 10.4049/jimmunol.1302021</ref>		<ref>Zhao, H., Anand, A. R., & Ganju, R. K. (2014). Slit2–Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia. The Journal of Immunology, 192(1), 385-393. PMID: 24272999 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908786/ PMC3908786] DOI: 10.4049/jimmunol.1302021</ref>
	<ref>Jones, C. A., Nishiya, N., London, N. R., Zhu, W., Sorensen, L. K., Chan, A. C., ... & Li, D. Y. (2009). Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology, 11(11), 1325-1331. PMID: 19855388 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854659/ PMC2854659] DOI: 10.1038/ncb1976</ref>		<ref>Jones, C. A., Nishiya, N., London, N. R., Zhu, W., Sorensen, L. K., Chan, A. C., ... & Li, D. Y. (2009). Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology, 11(11), 1325-1331. PMID: 19855388 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854659/ PMC2854659] DOI: 10.1038/ncb1976</ref>

Dmitry Dzhagarov at 16:23, 25 November 2023

2023-11-25T16:23:30Z

← Older revision		Revision as of 16:23, 25 November 2023
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	'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The cleaved N-terminal fragment of SLIT2, N-SLIT2, acts via its receptor, Roundabout guidance receptor 1 (ROBO1), to attenuate inflammasome activation in macrophages by inhibiting macropinocytosis.<ref>Bhosle, V. K., Mukherjee, T., Huang, Y. W., Patel, S., Pang, B. W., Liu, G. Y., ... & Robinson, L. A. (2020). SLIT2/ROBO1-signaling inhibits macropinocytosis by opposing cortical cytoskeletal remodeling. Nature communications, 11(1), 4112. PMID: 32807784 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431850/ PMC7431850] DOI: 10.1038/s41467-020-17651-1</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref> SLIT2 is located in chromosome 4p15.2 and encodes the human orthologue of the Drosophila Slit-2 protein.<ref>Georgas, K., Burridge, L., Smith, K., & Holmes, G. P. (1999). Assignment of the human slit homologue SLIT2 to human chromosome band 4p15. 2. Cytogenetic and Genome Research, 86(3/4), 246. PMID: 10575218 [https://doi.org/10.1159/000015351 DOI: 10.1159/000015351]</ref>		'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The cleaved N-terminal fragment of SLIT2, N-SLIT2, acts via its receptor, Roundabout guidance receptor 1 (ROBO1), to attenuate inflammasome activation in macrophages by inhibiting macropinocytosis.<ref>Bhosle, V. K., Mukherjee, T., Huang, Y. W., Patel, S., Pang, B. W., Liu, G. Y., ... & Robinson, L. A. (2020). SLIT2/ROBO1-signaling inhibits macropinocytosis by opposing cortical cytoskeletal remodeling. Nature communications, 11(1), 4112. PMID: 32807784 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431850/ PMC7431850] DOI: 10.1038/s41467-020-17651-1</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref> SLIT2 is located in chromosome 4p15.2 and encodes the human orthologue of the Drosophila Slit-2 protein.<ref>Georgas, K., Burridge, L., Smith, K., & Holmes, G. P. (1999). Assignment of the human slit homologue SLIT2 to human chromosome band 4p15. 2. Cytogenetic and Genome Research, 86(3/4), 246. PMID: 10575218 [https://doi.org/10.1159/000015351 DOI: 10.1159/000015351]</ref>
	Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.<ref>Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., ... & McCarthy, A. A. (2007). Structural insights into the Slit-Robo complex. Proceedings of the National Academy of Sciences, 104(38), 14923-14928. PMID: 17848514 PMCID: PMC1975871 DOI: 10.1073/pnas.0705310104</ref>		Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.<ref>Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., ... & McCarthy, A. A. (2007). Structural insights into the Slit-Robo complex. Proceedings of the National Academy of Sciences, 104(38), 14923-14928. PMID: 17848514 PMCID: PMC1975871 DOI: 10.1073/pnas.0705310104</ref> In vivo, Slit2 is cleaved into 140 kDa N-terminal (Slit2-N) and 55–60 kDa C-terminal (Slit2-C) fragments. Among them only recombinant Slit2-N showed a similar activity in stimulating branching and extension of dorsal root ganglia axons as reported for native Slit2-N purified from cells expressing wild-type full-length Slit2.<ref>Ba-Charvet, K. T. N., Brose, K., Ma, L., Wang, K. H., Marillat, V., Sotelo, C., ... & Chédotal, A. (2001). Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance. Journal of Neuroscience, 21(12), 4281-4289. PMID: 11404413 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762758/ PMC6762758] DOI: 10.1523/JNEUROSCI.21-12-04281.2001</ref>

	SLIT family is involved in the epithelial-mesenchymal transition process that permits cancer cells to acquire migratory, invasive, and stem-like properties.<ref>Basha, S., Jin-Smith, B., Sun, C., & Pi, L. (2023). The SLIT/ROBO Pathway in Liver Fibrosis and Cancer. Biomolecules, 13(5), 785. PMID: 37238655 PMCID: PMC10216401 DOI: 10.3390/biom13050785</ref>		SLIT family is involved in the epithelial-mesenchymal transition process that permits cancer cells to acquire migratory, invasive, and stem-like properties.<ref>Basha, S., Jin-Smith, B., Sun, C., & Pi, L. (2023). The SLIT/ROBO Pathway in Liver Fibrosis and Cancer. Biomolecules, 13(5), 785. PMID: 37238655 PMCID: PMC10216401 DOI: 10.3390/biom13050785</ref>

Dmitry Dzhagarov at 15:40, 25 November 2023

2023-11-25T15:40:17Z

← Older revision		Revision as of 15:40, 25 November 2023
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	'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref> SLIT2 is located in chromosome 4p15.2 and encodes the human orthologue of the Drosophila Slit-2 protein.<ref>Georgas, K., Burridge, L., Smith, K., & Holmes, G. P. (1999). Assignment of the human slit homologue SLIT2 to human chromosome band 4p15. 2. Cytogenetic and Genome Research, 86(3/4), 246. PMID: 10575218 [https://doi.org/10.1159/000015351 DOI: 10.1159/000015351]</ref>		'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The cleaved N-terminal fragment of SLIT2, N-SLIT2, acts via its receptor, Roundabout guidance receptor 1 (ROBO1), to attenuate inflammasome activation in macrophages by inhibiting macropinocytosis.<ref>Bhosle, V. K., Mukherjee, T., Huang, Y. W., Patel, S., Pang, B. W., Liu, G. Y., ... & Robinson, L. A. (2020). SLIT2/ROBO1-signaling inhibits macropinocytosis by opposing cortical cytoskeletal remodeling. Nature communications, 11(1), 4112. PMID: 32807784 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431850/ PMC7431850] DOI: 10.1038/s41467-020-17651-1</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref> SLIT2 is located in chromosome 4p15.2 and encodes the human orthologue of the Drosophila Slit-2 protein.<ref>Georgas, K., Burridge, L., Smith, K., & Holmes, G. P. (1999). Assignment of the human slit homologue SLIT2 to human chromosome band 4p15. 2. Cytogenetic and Genome Research, 86(3/4), 246. PMID: 10575218 [https://doi.org/10.1159/000015351 DOI: 10.1159/000015351]</ref>
	Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.<ref>Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., ... & McCarthy, A. A. (2007). Structural insights into the Slit-Robo complex. Proceedings of the National Academy of Sciences, 104(38), 14923-14928. PMID: 17848514 PMCID: PMC1975871 DOI: 10.1073/pnas.0705310104</ref>		Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.<ref>Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., ... & McCarthy, A. A. (2007). Structural insights into the Slit-Robo complex. Proceedings of the National Academy of Sciences, 104(38), 14923-14928. PMID: 17848514 PMCID: PMC1975871 DOI: 10.1073/pnas.0705310104</ref>

Dmitry Dzhagarov at 14:28, 25 November 2023

2023-11-25T14:28:57Z

← Older revision		Revision as of 14:28, 25 November 2023
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	<ref>Li, Q., Huang, L., Ding, Y., Sherchan, P., Peng, W., & Zhang, J. H. (2023). Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1–srGAP1 pathway in a rat model of germinal matrix hemorrhage. Journal of Neuroinflammation, 20(1), 249. PMID: 37899442 PMCID: PMC10613398 DOI: 10.1186/s12974-023-02935-2</ref>		<ref>Li, Q., Huang, L., Ding, Y., Sherchan, P., Peng, W., & Zhang, J. H. (2023). Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1–srGAP1 pathway in a rat model of germinal matrix hemorrhage. Journal of Neuroinflammation, 20(1), 249. PMID: 37899442 PMCID: PMC10613398 DOI: 10.1186/s12974-023-02935-2</ref>
	<ref>Li, X., Zheng, S., Tan, W., Chen, H., Li, X., Wu, J., ... & Yang, F. H. (2020). Slit2 protects hearts against ischemia-reperfusion injury by inhibiting inflammatory responses and maintaining myofilament contractile properties. Frontiers in physiology, 11, 228. PMID: 32292352 PMCID: PMC7135862 DOI: 10.3389/fphys.2020.00228</ref>		<ref>Li, X., Zheng, S., Tan, W., Chen, H., Li, X., Wu, J., ... & Yang, F. H. (2020). Slit2 protects hearts against ischemia-reperfusion injury by inhibiting inflammatory responses and maintaining myofilament contractile properties. Frontiers in physiology, 11, 228. PMID: 32292352 PMCID: PMC7135862 DOI: 10.3389/fphys.2020.00228</ref>
	<ref>Kim, Y. H., Lee, Y. K., Park, S. S., Park, S. H., Eom, S. Y., Lee, Y. S., ... & Park, T. J. (2023). Mid-old cells are a potential target for anti-aging interventions in the elderly. Nature Communications, 14(1), 7619. </ref>		<ref>Kim, Y. H., Lee, Y. K., Park, S. S., Park, S. H., Eom, S. Y., Lee, Y. S., ... & Park, T. J. (2023). Mid-old cells are a potential target for anti-aging interventions in the elderly. Nature Communications, 14(1), 7619. [https://doi.org/10.1038/s41467-023-43491-w DOI: 10.1038/s41467-023-43491-w]</ref>
	<ref>Zhao, H., Anand, A. R., & Ganju, R. K. (2014). Slit2–Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia. The Journal of Immunology, 192(1), 385-393. </ref>		<ref>Zhao, H., Anand, A. R., & Ganju, R. K. (2014). Slit2–Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia. The Journal of Immunology, 192(1), 385-393. PMID: 24272999 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908786/ PMC3908786] DOI: 10.4049/jimmunol.1302021</ref>
	<ref>Jones, C. A., Nishiya, N., London, N. R., Zhu, W., Sorensen, L. K., Chan, A. C., ... & Li, D. Y. (2009). Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology, 11(11), 1325-1331. PMID: 19855388 ~~PMCID~~: ~~PMC2854659 DOI: 10.1038~~/~~ncb1976<~~/~~ref>~~		<ref>Jones, C. A., Nishiya, N., London, N. R., Zhu, W., Sorensen, L. K., Chan, A. C., ... & Li, D. Y. (2009). Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology, 11(11), 1325-1331. PMID: 19855388 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854659/ PMC2854659] DOI: 10.1038/ncb1976</ref>

	~~During infection, Mycobacterium tuberculosis (Mtb) rewires distinct host signaling pathways that results in pathogen-favorable outcomes~~. ~~In particular induced expression of the neuronal ligand SLIT2 which was due to the Mtb-mediated phosphorylation of the P38/JNK pathways~~. ~~Activation of these kinases resulted in the loss of the repressive H3K27me3 signature on the Slit2 promoter~~.~~<ref>Borbora, S~~. M., Satish, B. A., Sundar, S., Bhatt, S., & Balaji, K. N. (2023). Mycobacterium tuberculosis elevates SLIT2 expression within the host and contributes to oxidative stress responses during infection. The Journal of Infectious Diseases, jiad126. PMID: 37158474 DOI: 10.~~1093~~/~~infdis/jiad126~~</ref> We noticed that many centenarians came from families where the incidence of tuberculosis was high (for example Jeanne Calment). This allows us to assume as a working hypothesis that perhaps activation of the Slit2 gene is involved in their longevity.

			During infection, Mycobacterium tuberculosis (Mtb) rewires distinct host signaling pathways that results in pathogen-favorable outcomes. In particular induced expression of the neuronal ligand SLIT2 which was due to the Mtb-mediated phosphorylation of the P38/JNK pathways. Activation of these kinases resulted in the loss of the repressive H3K27me3 signature on the Slit2 promoter.<ref>Borbora, S. M., Satish, B. A., Sundar, S., Bhatt, S., & Balaji, K. N. (2023). Mycobacterium tuberculosis elevates SLIT2 expression within the host and contributes to oxidative stress responses during infection. The Journal of Infectious Diseases, jiad126. PMID: 37158474 [https://doi.org/10.1093/infdis/jiad126 DOI: 10.1093/infdis/jiad126</ref> I noticed that many centenarians came from families where the incidence of tuberculosis was high (for example Jeanne Calment). This allows me to assume as a working hypothesis that perhaps activation of the Slit2 gene by Mtb is involved in their longevity.

			== References ==
			<references />
	[[Category:Longevity genes]]		[[Category:Longevity genes]]
	[[Category:Lifespan interventions]]		[[Category:Lifespan interventions]]
	[[Category:Main list]]		[[Category:Main list]]
	[[Category:Drafts]]		[[Category:Drafts]]

Dmitry Dzhagarov at 09:46, 25 November 2023

2023-11-25T09:46:08Z

← Older revision		Revision as of 09:46, 25 November 2023
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	'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref> SLIT2 is located in chromosome 4p15.2 and encodes the human orthologue of the Drosophila Slit-2 protein.<ref>Georgas, K., Burridge, L., Smith, K., & Holmes, G. P. (1999). Assignment of the human slit homologue SLIT2 to human chromosome band 4p15. 2. Cytogenetic and Genome Research, 86(3/4), 246. PMID: 10575218 [https://doi.org/10.1159/000015351 DOI: 10.1159/000015351]</ref>		'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref> SLIT2 is located in chromosome 4p15.2 and encodes the human orthologue of the Drosophila Slit-2 protein.<ref>Georgas, K., Burridge, L., Smith, K., & Holmes, G. P. (1999). Assignment of the human slit homologue SLIT2 to human chromosome band 4p15. 2. Cytogenetic and Genome Research, 86(3/4), 246. PMID: 10575218 [https://doi.org/10.1159/000015351 DOI: 10.1159/000015351]</ref>
	Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.		Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.<ref>Morlot, C., Thielens, N. M., Ravelli, R. B., Hemrika, W., Romijn, R. A., Gros, P., ... & McCarthy, A. A. (2007). Structural insights into the Slit-Robo complex. Proceedings of the National Academy of Sciences, 104(38), 14923-14928. PMID: 17848514 PMCID: PMC1975871 DOI: 10.1073/pnas.0705310104</ref>

	SLIT2 appears to function as a tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas.<ref>Jin, J., You, H., Yu, B., Deng, Y., Tang, N., Yao, G., ... & Qin, W. (2009). Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas. Biochemical and Biophysical Research Communications, 379(1), 86-91. PMID: 19100240 DOI: 10.1016/j.bbrc.2008.12.022</ref>		SLIT family is involved in the epithelial-mesenchymal transition process that permits cancer cells to acquire migratory, invasive, and stem-like properties.<ref>Basha, S., Jin-Smith, B., Sun, C., & Pi, L. (2023). The SLIT/ROBO Pathway in Liver Fibrosis and Cancer. Biomolecules, 13(5), 785. PMID: 37238655 PMCID: PMC10216401 DOI: 10.3390/biom13050785</ref>
			SLIT2 appears to function as a tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas.<ref>Jin, J., You, H., Yu, B., Deng, Y., Tang, N., Yao, G., ... & Qin, W. (2009). Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas. Biochemical and Biophysical Research Communications, 379(1), 86-91. PMID: 19100240 DOI: 10.1016/j.bbrc.2008.12.022</ref>

Dmitry Dzhagarov at 09:31, 25 November 2023

2023-11-25T09:31:39Z

← Older revision		Revision as of 09:31, 25 November 2023
Line 1:		Line 1:
	'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref>		'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref> SLIT2 is located in chromosome 4p15.2 and encodes the human orthologue of the Drosophila Slit-2 protein.<ref>Georgas, K., Burridge, L., Smith, K., & Holmes, G. P. (1999). Assignment of the human slit homologue SLIT2 to human chromosome band 4p15. 2. Cytogenetic and Genome Research, 86(3/4), 246. PMID: 10575218 [https://doi.org/10.1159/000015351 DOI: 10.1159/000015351]</ref>
	Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.		Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.

Dmitry Dzhagarov: Created page with "'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 285..."

2023-11-25T08:58:39Z

Created page with "'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 285..."

New page

'''SLIT2''' (Slit Guidance Ligand 2) is a protein coding gene that encode large secreted protein functioning as ligand for '''Roundabout (Robo)''' receptors.<ref>Blockus, H., & Chédotal, A. (2016). Slit-robo signaling. Development, 143(17), 3037-3044. PMID: 27578174 DOI: 10.1242/dev.132829</ref><ref>Wu, M. F., Liao, C. Y., Wang, L. Y., & Chang, J. T. (2017). The role of Slit-Robo signaling in the regulation of tissue barriers. Tissue Barriers, 5(2), e1331155. PMID: 28598714 PMCID: PMC5501134 DOI: 10.1080/21688370.2017.1331155</ref> The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins.<ref>Little, M., Rumballe, B., Georgas, K., Yamada, T., & Teasdale, R. D. (2004). Conserved modularity and potential for alternate splicing in mouse and human Slit genes. International Journal of Developmental Biology, 46(4), 385-391.</ref><ref>Piper, M., & Little, M. (2003). Movement through Slits: cellular migration via the Slit family. Bioessays, 25(1), 32-38. PMID: 12508280 DOI: 10.1002/bies.10199</ref><ref>Wong, K., Park, H. T., Wu, J. Y., & Rao, Y. (2002). Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Current opinion in genetics & development, 12(5), 583-591. PMID: 12200164 DOI: 10.1016/s0959-437x(02)00343-x</ref>
Slit was identified in ''Drosophila'' embryo as a gene involved in the patterning of larval cuticle. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells. Slit homologues have since been found in many vertebrate species, from amphibians, fishes, birds to mammals. There are three slit genes (slit1-slit3) in mammals, that have around 60% homology. All encodes large Extracellular matrix glycoproteins of about 200 kDa, comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF (epidermal growth factor-like domain) repeats, laminin G-like module - a domain, named ALPS (Agrin, Perlecan, Laminin, Slit), and a cystein knot.

SLIT2 appears to function as a tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas.<ref>Jin, J., You, H., Yu, B., Deng, Y., Tang, N., Yao, G., ... & Qin, W. (2009). Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas. Biochemical and Biophysical Research Communications, 379(1), 86-91. PMID: 19100240 DOI: 10.1016/j.bbrc.2008.12.022</ref>

<ref>Dallol, A., Da Silva, N. F., Viacava, P., Minna, J. D., Bieche, I., Maher, E. R., & Latif, F. (2002). SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers. Cancer research, 62(20), 5874-5880. PMID: 12384551</ref>
<ref>Liu, J. W., Liu, H. T., & Chen, L. (2021). The therapeutic role of Slit2 in anti-fibrosis, anti-inflammation and anti-oxidative stress in rats with coronary heart disease. Cardiovascular Toxicology, 21(12), 973-983. PMID: 34410632 DOI: 10.1007/s12012-021-09688-5</ref>
<ref>Li, Q., Huang, L., Ding, Y., Sherchan, P., Peng, W., & Zhang, J. H. (2023). Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1–srGAP1 pathway in a rat model of germinal matrix hemorrhage. Journal of Neuroinflammation, 20(1), 249. PMID: 37899442 PMCID: PMC10613398 DOI: 10.1186/s12974-023-02935-2</ref>
<ref>Li, X., Zheng, S., Tan, W., Chen, H., Li, X., Wu, J., ... & Yang, F. H. (2020). Slit2 protects hearts against ischemia-reperfusion injury by inhibiting inflammatory responses and maintaining myofilament contractile properties. Frontiers in physiology, 11, 228. PMID: 32292352 PMCID: PMC7135862 DOI: 10.3389/fphys.2020.00228</ref>
<ref>Kim, Y. H., Lee, Y. K., Park, S. S., Park, S. H., Eom, S. Y., Lee, Y. S., ... & Park, T. J. (2023). Mid-old cells are a potential target for anti-aging interventions in the elderly. Nature Communications, 14(1), 7619. </ref>
<ref>Zhao, H., Anand, A. R., & Ganju, R. K. (2014). Slit2–Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia. The Journal of Immunology, 192(1), 385-393. </ref>
<ref>Jones, C. A., Nishiya, N., London, N. R., Zhu, W., Sorensen, L. K., Chan, A. C., ... & Li, D. Y. (2009). Slit2–Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nature cell biology, 11(11), 1325-1331. PMID: 19855388 PMCID: PMC2854659 DOI: 10.1038/ncb1976</ref>

During infection, Mycobacterium tuberculosis (Mtb) rewires distinct host signaling pathways that results in pathogen-favorable outcomes. In particular induced expression of the neuronal ligand SLIT2 which was due to the Mtb-mediated phosphorylation of the P38/JNK pathways. Activation of these kinases resulted in the loss of the repressive H3K27me3 signature on the Slit2 promoter.<ref>Borbora, S. M., Satish, B. A., Sundar, S., Bhatt, S., & Balaji, K. N. (2023). Mycobacterium tuberculosis elevates SLIT2 expression within the host and contributes to oxidative stress responses during infection. The Journal of Infectious Diseases, jiad126. PMID: 37158474 DOI: 10.1093/infdis/jiad126</ref> We noticed that many centenarians came from families where the incidence of tuberculosis was high (for example Jeanne Calment). This allows us to assume as a working hypothesis that perhaps activation of the Slit2 gene is involved in their longevity.

[[Category:Longevity genes]]
[[Category:Lifespan interventions]]
[[Category:Main list]]
[[Category:Drafts]]