Ball Stephen G, Shuttleworth C Adrian, Kielty Cay M
UK Centre for Tissue Engineering, Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Int J Biochem Cell Biol. 2007;39(2):379-91. doi: 10.1016/j.biocel.2006.09.005. Epub 2006 Sep 24.
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.
平滑肌α-肌动蛋白丝是间充质干细胞以及间充质来源的收缩性平滑肌细胞、周细胞和成肌纤维细胞的一个决定性特征。在此，我们表明，成年骨髓来源的间充质干细胞表达丰富的细胞表面血小板衍生生长因子受体-α，与血小板衍生生长因子受体-β的比例很高。通过血小板衍生生长因子受体-α的信号传导通过激活RhoA增加平滑肌α-肌动蛋白丝，这导致Rho相关激酶（ROCK）依赖性的丝切蛋白磷酸化，增强平滑肌α-肌动蛋白丝的聚合，并且还上调平滑肌α-肌动蛋白的表达。相反，血小板衍生生长因子受体-β信号传导强烈上调RhoE，其抑制ROCK活性，促进平滑肌α-肌动蛋白丝的解聚。因此，本研究为血小板衍生生长因子受体-α和-β信号传导在调节成年间充质干细胞收缩性细胞骨架中的不同作用提供了新的见解。
