Platelet-derived growth factor receptor-α is a key determinant of smooth muscle α-actin filaments in bone marrow-derived mesenchymal stem cells

被引:56
作者
Ball, Stephen G.
Shuttleworth, C. Adrian
Kielty, Cay M.
机构
[1] Univ Manchester, UK Ctr Tissue Engn, Fac Life Sci, Manchester M13 9PT, Lancs, England
[2] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Fac Life Sci, Manchester M13 9PT, Lancs, England
基金
英国医学研究理事会;
关键词
human mesenchymal stem cells; platelet-derived growth factor receptor-alpha; smooth muscle alpha-actin; RhoA; cell signaling;
D O I
10.1016/j.biocel.2006.09.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Smooth muscle alpha-actin filaments are a defining feature of mesenchymal stem cells, and of mesenchyme-derived contractile smooth muscle cells. pericytes and myofibroblasts. Here, we show that adult bone marrow-derived mesenchymal stem cells express abundant cell surface platelet-derived growth factor receptor-alpha, having a high ratio to platelet-derived growth factor receptor-beta. Signaling through platelet-derived growth factor receptor-alpha increases smooth muscle alpha-actin filaments by activating RhoA, which results in Rho-associated kinase (ROCK)-dependent cofilin phosphorylation, enhancing smooth muscle alpha-actin filament polymerization, and also upregulates smooth muscle alpha-actin expression. In contrast, platelet-derived growth factor receptor-beta signaling strongly upregulates RhoE, which inhibits ROCK activity, promoting smooth muscle alpha-actin filament depolymerization. This study thus provides new insights into the distinct roles of platelet-derived growth factor receptor-alpha and -beta signaling in regulating the adult mesenchymal stem cell contractile cytoskeleton. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:379 / 391
页数:13
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