A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.

CD248 (Endosialin) is a type 1 membrane protein involved in developmental and pathological angiogenesis through its expression on pericytes and regulation of PDGFRβ signalling. Here we explore the function of CD248 in skeletal muscle angiogenesis. Two distinct forms of capillary growth (splitting an...

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Autores principales:	Amy J Naylor, Helen M McGettrick, William D Maynard, Philippa May, Francesca Barone, Adam P Croft, Stuart Egginton, Christopher D Buckley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/891a64c1198f4ce3ab1690c7bde40890
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spelling	oai:doaj.org-article:891a64c1198f4ce3ab1690c7bde408902021-11-25T05:59:53ZA differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.1932-620310.1371/journal.pone.0107146https://doaj.org/article/891a64c1198f4ce3ab1690c7bde408902014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107146https://doaj.org/toc/1932-6203CD248 (Endosialin) is a type 1 membrane protein involved in developmental and pathological angiogenesis through its expression on pericytes and regulation of PDGFRβ signalling. Here we explore the function of CD248 in skeletal muscle angiogenesis. Two distinct forms of capillary growth (splitting and sprouting) can be induced separately by increasing microcirculatory shear stress (chronic vasodilator treatment) or by inducing functional overload (extirpation of a synergistic muscle). We show that CD248 is present on pericytes in muscle and that CD248-/- mice have a specific defect in capillary sprouting. In contrast, splitting angiogenesis is independent of CD248 expression. Endothelial cells respond to pro-sprouting angiogenic stimulus by up-regulating gene expression for HIF1α, angiopoietin 2 and its receptor TEK, PDGF-B and its receptor PDGFRβ; this response did not occur following a pro-splitting angiogenic stimulus. In wildtype mice, defective sprouting angiogenesis could be mimicked by blocking PDGFRβ signalling using the tyrosine kinase inhibitor Imatinib mesylate. We conclude that CD248 is required for PDGFRβ-dependant capillary sprouting but not splitting angiogenesis, and identify a new role for CD248 expressed on pericytes in the early stages of physiological angiogenesis during muscle remodelling.Amy J NaylorHelen M McGettrickWilliam D MaynardPhilippa MayFrancesca BaroneAdam P CroftStuart EggintonChristopher D BuckleyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107146 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amy J Naylor Helen M McGettrick William D Maynard Philippa May Francesca Barone Adam P Croft Stuart Egginton Christopher D Buckley A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.
description	CD248 (Endosialin) is a type 1 membrane protein involved in developmental and pathological angiogenesis through its expression on pericytes and regulation of PDGFRβ signalling. Here we explore the function of CD248 in skeletal muscle angiogenesis. Two distinct forms of capillary growth (splitting and sprouting) can be induced separately by increasing microcirculatory shear stress (chronic vasodilator treatment) or by inducing functional overload (extirpation of a synergistic muscle). We show that CD248 is present on pericytes in muscle and that CD248-/- mice have a specific defect in capillary sprouting. In contrast, splitting angiogenesis is independent of CD248 expression. Endothelial cells respond to pro-sprouting angiogenic stimulus by up-regulating gene expression for HIF1α, angiopoietin 2 and its receptor TEK, PDGF-B and its receptor PDGFRβ; this response did not occur following a pro-splitting angiogenic stimulus. In wildtype mice, defective sprouting angiogenesis could be mimicked by blocking PDGFRβ signalling using the tyrosine kinase inhibitor Imatinib mesylate. We conclude that CD248 is required for PDGFRβ-dependant capillary sprouting but not splitting angiogenesis, and identify a new role for CD248 expressed on pericytes in the early stages of physiological angiogenesis during muscle remodelling.
format	article
author	Amy J Naylor Helen M McGettrick William D Maynard Philippa May Francesca Barone Adam P Croft Stuart Egginton Christopher D Buckley
author_facet	Amy J Naylor Helen M McGettrick William D Maynard Philippa May Francesca Barone Adam P Croft Stuart Egginton Christopher D Buckley
author_sort	Amy J Naylor
title	A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.
title_short	A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.
title_full	A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.
title_fullStr	A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.
title_full_unstemmed	A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.
title_sort	differential role for cd248 (endosialin) in pdgf-mediated skeletal muscle angiogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/891a64c1198f4ce3ab1690c7bde40890
work_keys_str_mv	AT amyjnaylor adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT helenmmcgettrick adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT williamdmaynard adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT philippamay adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT francescabarone adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT adampcroft adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT stuartegginton adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT christopherdbuckley adifferentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT amyjnaylor differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT helenmmcgettrick differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT williamdmaynard differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT philippamay differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT francescabarone differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT adampcroft differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT stuartegginton differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis AT christopherdbuckley differentialroleforcd248endosialininpdgfmediatedskeletalmuscleangiogenesis
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A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.

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