A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis

Abstract Crohn’s disease and ulcerative colitis are the two forms of disorders of the human inflammatory bowel disease with unknown etiologies. Endothelial cell protein C receptor (EPCR) is a multifunctional and multiligand receptor, which is expressed on the endothelium and other cell types, includ...

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Autores principales:	Vijay Kondreddy, Shiva Keshava, Charles T. Esmon, Usha R. Pendurthi, L. Vijaya Mohan Rao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85c508b614b942408bc8046a59867658
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spelling	oai:doaj.org-article:85c508b614b942408bc8046a598676582021-12-02T11:40:20ZA critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis10.1038/s41598-020-77502-32045-2322https://doaj.org/article/85c508b614b942408bc8046a598676582020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77502-3https://doaj.org/toc/2045-2322Abstract Crohn’s disease and ulcerative colitis are the two forms of disorders of the human inflammatory bowel disease with unknown etiologies. Endothelial cell protein C receptor (EPCR) is a multifunctional and multiligand receptor, which is expressed on the endothelium and other cell types, including epithelial cells. Here, we report that EPCR is expressed in the colon epithelial cells, CD11c+, and CD21+/CD35+ myeloid cells surrounding the crypts in the colon mucosa. EPCR expression was markedly decreased in the colon mucosa during colitis. The loss of EPCR appeared to associate with increased disease index of the experimental colitis in mice. EPCR−/− mice were more susceptible to dextran sulfate sodium (DSS)-induced colitis, manifested by increased weight loss, macrophage infiltration, and inflammatory cytokines in the colon tissue. DSS treatment of EPCR−/− mice resulted in increased bleeding, bodyweight loss, anemia, fibrin deposition, and loss of colon epithelial and goblet cells. Administration of coagulant factor VIIa significantly attenuated the DSS-induced colon length shortening, rectal bleeding, bodyweight loss, and disease activity index in the wild-type mice but not EPCR−/− mice. In summary, our data provide direct evidence that EPCR plays a crucial role in regulating the inflammation in the colon during colitis.Vijay KondreddyShiva KeshavaCharles T. EsmonUsha R. PendurthiL. Vijaya Mohan RaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vijay Kondreddy Shiva Keshava Charles T. Esmon Usha R. Pendurthi L. Vijaya Mohan Rao A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis
description	Abstract Crohn’s disease and ulcerative colitis are the two forms of disorders of the human inflammatory bowel disease with unknown etiologies. Endothelial cell protein C receptor (EPCR) is a multifunctional and multiligand receptor, which is expressed on the endothelium and other cell types, including epithelial cells. Here, we report that EPCR is expressed in the colon epithelial cells, CD11c+, and CD21+/CD35+ myeloid cells surrounding the crypts in the colon mucosa. EPCR expression was markedly decreased in the colon mucosa during colitis. The loss of EPCR appeared to associate with increased disease index of the experimental colitis in mice. EPCR−/− mice were more susceptible to dextran sulfate sodium (DSS)-induced colitis, manifested by increased weight loss, macrophage infiltration, and inflammatory cytokines in the colon tissue. DSS treatment of EPCR−/− mice resulted in increased bleeding, bodyweight loss, anemia, fibrin deposition, and loss of colon epithelial and goblet cells. Administration of coagulant factor VIIa significantly attenuated the DSS-induced colon length shortening, rectal bleeding, bodyweight loss, and disease activity index in the wild-type mice but not EPCR−/− mice. In summary, our data provide direct evidence that EPCR plays a crucial role in regulating the inflammation in the colon during colitis.
format	article
author	Vijay Kondreddy Shiva Keshava Charles T. Esmon Usha R. Pendurthi L. Vijaya Mohan Rao
author_facet	Vijay Kondreddy Shiva Keshava Charles T. Esmon Usha R. Pendurthi L. Vijaya Mohan Rao
author_sort	Vijay Kondreddy
title	A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis
title_short	A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis
title_full	A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis
title_fullStr	A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis
title_full_unstemmed	A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis
title_sort	critical role of endothelial cell protein c receptor in the intestinal homeostasis in experimental colitis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/85c508b614b942408bc8046a59867658
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A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis

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