Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of α-smooth muscle action filaments during myofibroblast differentiation

Academic Article

Abstract

  • Myofibroblasts are implicated in pathological stromal responses associated with lung fibrosis. One prominent phenotypic marker of fully differentiated myofibroblasts is the polymerized, thick cytoplasmic filaments containing newly synthesized α-smooth muscle action (α-SMA). These α-SMA-containing cytoplasmic filaments are important for myofibroblast contractility during tissue remodeling. However, the molecular mechanisms regulating the formation and maturation of α-SMA-containing filaments have not been defined. This study demonstrates a critical role for neuronal Wiskott-Aldrich syndrome protein (N-WASP) in regulating the formation of a-SMA-containing cytoplasmic filaments during myofibroblast differentiation and in myofibroblast contractility. Focal adhesion kinase (FAK) is activated by transforming growth factor-β1 (TGF-β1) and is required for phosphorylation of tyrosine residue 256 (Y256) of N-WASP. Phosphorylation of Y256 of N-WASP is essential for TGF-β1-induced formation of a-SMA-containing cytoplasmic filaments in primary human lung fibroblasts. In addition, we demonstrate that action-related protein (Arp) 2/3 complex is downstream of N-WASP and mediates the maturation of α-SMA-containing cytoplasmic filaments. Together, this study supports a critical role of N-WASP in integrating FAK and Arp2/3 signaling to mediate formation of α-SMA-containing cytoplasmic filaments during myofibroblast differentiation and maturation. © 2012 the American Physiological Society.
  • Digital Object Identifier (doi)

    Author List

  • Cai GQ; Chou CF; Hu M; Zheng A; Reichardt LF; Guan JL; Fang H; Luckhardt TR; Zhou Y; Thannickal VJ
  • Volume

  • 303
  • Issue

  • 8