Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy

Abstract CYR61-CTGF-NOV (CCN)1 is a dynamically expressed extracellular matrix (ECM) protein with critical functions in cardiovascular development and tissue repair. Angiogenic endothelial cells (ECs) are a major cellular source of CCN1 which, once secreted, associates with the ECM and the cell surf...

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Autores principales:	Sangmi Lee, Menna Elaskandrany, Lester F. Lau, Douglas Lazzaro, Maria B. Grant, Brahim Chaqour
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/081b1e69b3a246369c5c4a860c3ee750
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spelling	oai:doaj.org-article:081b1e69b3a246369c5c4a860c3ee7502021-12-02T12:32:42ZInterplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy10.1038/s41598-017-01585-82045-2322https://doaj.org/article/081b1e69b3a246369c5c4a860c3ee7502017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01585-8https://doaj.org/toc/2045-2322Abstract CYR61-CTGF-NOV (CCN)1 is a dynamically expressed extracellular matrix (ECM) protein with critical functions in cardiovascular development and tissue repair. Angiogenic endothelial cells (ECs) are a major cellular source of CCN1 which, once secreted, associates with the ECM and the cell surface and tightly controls the bidirectional flow of information between cells and the surrounding matrix. Endothelium-specific CCN1 deletion in mice using a cre/lox strategy induces EC hyperplasia and causes blood vessels to coalesce into large flat hyperplastic sinuses with no distinctive hierarchical organization. This is consistent with the role of CCN1 as a negative feedback regulator of vascular endothelial growth factor (VEGF) receptor activation. In the mouse model of oxygen-induced retinopathy (OIR), pericytes become the predominant CCN1 producing cells. Pericyte-specific deletion of CCN1 significantly decreases pathological retinal neovascularization following OIR. CCN1 induces the expression of the non-canonical Wnt5a in pericyte but not in EC cultures. In turn, exogenous Wnt5a inhibits CCN1 gene expression, induces EC proliferation and increases hypersprouting. Concordantly, treatment of mice with TNP470, a non-canonical Wnt5a inhibitor, reestablishes endothelial expression of CCN1 and significantly decreases pathological neovascular growth in OIR. Our data highlight the significance of CCN1-EC and CCN1-pericyte communication signals in driving physiological and pathological angiogenesis.Sangmi LeeMenna ElaskandranyLester F. LauDouglas LazzaroMaria B. GrantBrahim ChaqourNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sangmi Lee Menna Elaskandrany Lester F. Lau Douglas Lazzaro Maria B. Grant Brahim Chaqour Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy
description	Abstract CYR61-CTGF-NOV (CCN)1 is a dynamically expressed extracellular matrix (ECM) protein with critical functions in cardiovascular development and tissue repair. Angiogenic endothelial cells (ECs) are a major cellular source of CCN1 which, once secreted, associates with the ECM and the cell surface and tightly controls the bidirectional flow of information between cells and the surrounding matrix. Endothelium-specific CCN1 deletion in mice using a cre/lox strategy induces EC hyperplasia and causes blood vessels to coalesce into large flat hyperplastic sinuses with no distinctive hierarchical organization. This is consistent with the role of CCN1 as a negative feedback regulator of vascular endothelial growth factor (VEGF) receptor activation. In the mouse model of oxygen-induced retinopathy (OIR), pericytes become the predominant CCN1 producing cells. Pericyte-specific deletion of CCN1 significantly decreases pathological retinal neovascularization following OIR. CCN1 induces the expression of the non-canonical Wnt5a in pericyte but not in EC cultures. In turn, exogenous Wnt5a inhibits CCN1 gene expression, induces EC proliferation and increases hypersprouting. Concordantly, treatment of mice with TNP470, a non-canonical Wnt5a inhibitor, reestablishes endothelial expression of CCN1 and significantly decreases pathological neovascular growth in OIR. Our data highlight the significance of CCN1-EC and CCN1-pericyte communication signals in driving physiological and pathological angiogenesis.
format	article
author	Sangmi Lee Menna Elaskandrany Lester F. Lau Douglas Lazzaro Maria B. Grant Brahim Chaqour
author_facet	Sangmi Lee Menna Elaskandrany Lester F. Lau Douglas Lazzaro Maria B. Grant Brahim Chaqour
author_sort	Sangmi Lee
title	Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy
title_short	Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy
title_full	Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy
title_fullStr	Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy
title_full_unstemmed	Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy
title_sort	interplay between ccn1 and wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/081b1e69b3a246369c5c4a860c3ee750
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Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy

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