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ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions

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Názov: ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions
Autori: Chang, Garry H. K., Lay, Angelina J., Ting, Ka Ka, Zhao, Yang, Coleman, Paul R., Powter, Elizabeth E., Formaz-Preston, Ann, Jolly,Christopher J., Bower, Neil I., Hogan, Benjamin M., Rinkwitz, Silke, Becker, Thomas S., Vardas, Mathew A., Gamble, Jennifer R.
Zdroj: Small GTPases. 5:e975002
Informácie o vydavateľovi: Informa UK Limited, 2014.
Rok vydania: 2014
Predmety: rho GTP-Binding Proteins, 0301 basic medicine, 1303 Biochemistry, Melanoma, Experimental, Neovascularization, Physiologic, Retina, 1307 Cell Biology, Cell junctions, Mice, 03 medical and health sciences, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, Animals, Humans, Arhgap18, Zebrafish, 0303 health sciences, GTPase-Activating Proteins, Endothelial Cells, Senex, Zebrafish Proteins, 3. Good health, Mice, Inbred C57BL, Intercellular Junctions, 13. Climate action, Angiogenesis, Sprouting
Popis: The formation of the vascular network requires a tightly controlled balance of pro-angiogenic and stabilizing signals. Perturbation of this balance can result in dysregulated blood vessel morphogenesis and drive pathologies including cancer. Here, we have identified a novel gene, ARHGAP18, as an endogenous negative regulator of angiogenesis, limiting pro-angiogenic signaling and promoting vascular stability. Loss of ARHGAP18 promotes EC hypersprouting during zebrafish and murine retinal vessel development and enhances tumor vascularization and growth. Endogenous ARHGAP18 acts specifically on RhoC and relocalizes to the angiogenic and destabilized EC junctions in a ROCK dependent manner, where it is important in reaffirming stable EC junctions and suppressing tip cell behavior, at least partially through regulation of tip cell genes, Dll4, Flk-1 and Flt-4. These findings highlight ARHGAP18 as a specific RhoGAP to fine tune vascular morphogenesis, limiting tip cell formation and promoting junctional integrity to stabilize the angiogenic architecture.
Druh dokumentu: Article
Jazyk: English
ISSN: 2154-1256
2154-1248
DOI: 10.4161/21541248.2014.975002
Prístupová URL adresa: https://www.tandfonline.com/doi/pdf/10.4161/21541248.2014.975002?needAccess=true
https://pubmed.ncbi.nlm.nih.gov/25425145
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601187/
https://europepmc.org/abstract/MED/25425145
https://core.ac.uk/display/43362365
https://www.tandfonline.com/doi/full/10.4161/21541248.2014.975002
https://www.tandfonline.com/doi/pdf/10.4161/21541248.2014.975002
https://espace.library.uq.edu.au/view/UQ:349170
Prístupové číslo: edsair.doi.dedup.....f4898812bc1a0894b9403861adb0ff5b
Databáza: OpenAIRE
Popis
Abstrakt:The formation of the vascular network requires a tightly controlled balance of pro-angiogenic and stabilizing signals. Perturbation of this balance can result in dysregulated blood vessel morphogenesis and drive pathologies including cancer. Here, we have identified a novel gene, ARHGAP18, as an endogenous negative regulator of angiogenesis, limiting pro-angiogenic signaling and promoting vascular stability. Loss of ARHGAP18 promotes EC hypersprouting during zebrafish and murine retinal vessel development and enhances tumor vascularization and growth. Endogenous ARHGAP18 acts specifically on RhoC and relocalizes to the angiogenic and destabilized EC junctions in a ROCK dependent manner, where it is important in reaffirming stable EC junctions and suppressing tip cell behavior, at least partially through regulation of tip cell genes, Dll4, Flk-1 and Flt-4. These findings highlight ARHGAP18 as a specific RhoGAP to fine tune vascular morphogenesis, limiting tip cell formation and promoting junctional integrity to stabilize the angiogenic architecture.
ISSN:21541256
21541248
DOI:10.4161/21541248.2014.975002