G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin

Abstract Thrombomodulin (TM) stimulates angiogenesis and protects vascular endothelial cells (ECs) via its fifth epidermal growth factor-like region (TME5); however, the cell surface receptor that mediates the pro-survival signaling activated by TM has remained unknown. We applied pull-down assay fo...

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Autores principales:	Bin Pan, Xiangmin Wang, Chie Nishioka, Goichi Honda, Akihito Yokoyama, Lingyu Zeng, Kailin Xu, Takayuki Ikezoe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd8c9b4f5e79444090f11c54054dee9b
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spelling	oai:doaj.org-article:cd8c9b4f5e79444090f11c54054dee9b2021-12-02T12:32:57ZG-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin10.1038/s41598-017-00781-w2045-2322https://doaj.org/article/cd8c9b4f5e79444090f11c54054dee9b2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00781-whttps://doaj.org/toc/2045-2322Abstract Thrombomodulin (TM) stimulates angiogenesis and protects vascular endothelial cells (ECs) via its fifth epidermal growth factor-like region (TME5); however, the cell surface receptor that mediates the pro-survival signaling activated by TM has remained unknown. We applied pull-down assay followed by MALDI-TOF MS and western blot analysis, and identified G-protein coupled receptor 15 (GPR15) as a binding partner of TME5. TME5 rescued growth inhibition and apoptosis caused by calcineurin inhibitor FK506 in vascular ECs isolated from wild type (WT) C57BL/6 mice. On the other hand, TME5 failed to protect ECs isolated from GPR15 knockout (GPR15 KO) mice from FK506-caused vascular injury. TME5 induced activation of extracellular signal-regulated kinase (ERK) and increased level of anti-apoptotic proteins in a GPR15 dependent manner. In addition, in vivo Matrigel plug angiogenesis assay found that TME5 stimulated angiogenesis in mice. TME5 promoted endothelial migration in vitro. Furthermore, TME5 increased production of NO in association with activated endothelial NO synthase (eNOS) in ECs. All these pro-angiogenesis functions of TME5 were abolished by knockout of GPR15. Our findings suggest that GPR15 plays an important role in mediating cytoprotective function as well as angiogenesis of TM.Bin PanXiangmin WangChie NishiokaGoichi HondaAkihito YokoyamaLingyu ZengKailin XuTakayuki IkezoeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bin Pan Xiangmin Wang Chie Nishioka Goichi Honda Akihito Yokoyama Lingyu Zeng Kailin Xu Takayuki Ikezoe G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
description	Abstract Thrombomodulin (TM) stimulates angiogenesis and protects vascular endothelial cells (ECs) via its fifth epidermal growth factor-like region (TME5); however, the cell surface receptor that mediates the pro-survival signaling activated by TM has remained unknown. We applied pull-down assay followed by MALDI-TOF MS and western blot analysis, and identified G-protein coupled receptor 15 (GPR15) as a binding partner of TME5. TME5 rescued growth inhibition and apoptosis caused by calcineurin inhibitor FK506 in vascular ECs isolated from wild type (WT) C57BL/6 mice. On the other hand, TME5 failed to protect ECs isolated from GPR15 knockout (GPR15 KO) mice from FK506-caused vascular injury. TME5 induced activation of extracellular signal-regulated kinase (ERK) and increased level of anti-apoptotic proteins in a GPR15 dependent manner. In addition, in vivo Matrigel plug angiogenesis assay found that TME5 stimulated angiogenesis in mice. TME5 promoted endothelial migration in vitro. Furthermore, TME5 increased production of NO in association with activated endothelial NO synthase (eNOS) in ECs. All these pro-angiogenesis functions of TME5 were abolished by knockout of GPR15. Our findings suggest that GPR15 plays an important role in mediating cytoprotective function as well as angiogenesis of TM.
format	article
author	Bin Pan Xiangmin Wang Chie Nishioka Goichi Honda Akihito Yokoyama Lingyu Zeng Kailin Xu Takayuki Ikezoe
author_facet	Bin Pan Xiangmin Wang Chie Nishioka Goichi Honda Akihito Yokoyama Lingyu Zeng Kailin Xu Takayuki Ikezoe
author_sort	Bin Pan
title	G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
title_short	G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
title_full	G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
title_fullStr	G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
title_full_unstemmed	G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
title_sort	g-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cd8c9b4f5e79444090f11c54054dee9b
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G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin

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