Document Detail


Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of α-smooth muscle actin filaments during myofibroblast differentiation.
MedLine Citation:
PMID:  22886502     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 actin (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 α-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 α-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 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.
Authors:
Guo-Qiang Cai; Chu-Fang Chou; Meng Hu; Anni Zheng; Louis F Reichardt; Jun-Lin Guan; Haotian Fang; Tracy R Luckhardt; Yong Zhou; Victor J Thannickal; Qiang Ding
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-10
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  303     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-16     Completed Date:  2012-12-26     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L692-702     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / drug effects,  metabolism*
Actin-Related Protein 3 / metabolism
Actins / metabolism*
Animals
Cell Differentiation / drug effects,  physiology
Collagen / metabolism
Cytoplasm / metabolism
Fibroblasts / cytology,  metabolism*
Focal Adhesion Kinase 1 / metabolism
Lung / cytology,  metabolism
Mice
Mice, Inbred C57BL
Phosphorylation / drug effects,  physiology
Primary Cell Culture
Pulmonary Fibrosis / metabolism*,  pathology
RNA, Small Interfering / genetics
Transforming Growth Factor beta1 / pharmacology
Tyrosine / metabolism
Wiskott-Aldrich Syndrome Protein, Neuronal / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
HL085324/HL/NHLBI NIH HHS; HL095451/HL/NHLBI NIH HHS; K08 HL094666/HL/NHLBI NIH HHS; R01 HL085324/HL/NHLBI NIH HHS; R03 HL095451/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Actin-Related Protein 3; 0/Actins; 0/Actr3 protein, mouse; 0/RNA, Small Interfering; 0/Transforming Growth Factor beta1; 0/Wasl protein, mouse; 0/Wiskott-Aldrich Syndrome Protein, Neuronal; 0/alpha-smooth muscle actin, mouse; 42HK56048U/Tyrosine; 9007-34-5/Collagen; EC 2.7.10.2/Focal Adhesion Kinase 1; EC 2.7.10.2/Ptk2 protein, mouse
Comments/Corrections

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