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

Abstract

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.