| First Author | Cai GQ | Year | 2012 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 303 |
| Issue | 8 | Pages | L692-702 |
| PubMed ID | 22886502 | Mgi Jnum | J:330525 |
| Mgi Id | MGI:6854930 | Doi | 10.1152/ajplung.00390.2011 |
| Citation | Cai GQ, et al. (2012) Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of alpha-smooth muscle actin filaments during myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol 303(8):L692-702 |
| abstractText | 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 alpha-smooth muscle actin (alpha-SMA). These alpha-SMA-containing cytoplasmic filaments are important for myofibroblast contractility during tissue remodeling. However, the molecular mechanisms regulating the formation and maturation of alpha-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 alpha-SMA-containing cytoplasmic filaments during myofibroblast differentiation and in myofibroblast contractility. Focal adhesion kinase (FAK) is activated by transforming growth factor-beta1 (TGF-beta1) and is required for phosphorylation of tyrosine residue 256 (Y256) of N-WASP. Phosphorylation of Y256 of N-WASP is essential for TGF-beta1-induced formation of alpha-SMA-containing cytoplasmic filaments in primary human lung fibroblasts. In addition, we demonstrate that actin-related protein (Arp) 2/3 complex is downstream of N-WASP and mediates the maturation of alpha-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 alpha-SMA-containing cytoplasmic filaments during myofibroblast differentiation and maturation. |
