| Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of α-smooth muscle actin filaments during myofibroblast differentiation. | |
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MedLine Citation:
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PMID: 22886502 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-08-10 |
Journal Detail:
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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:
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Created Date: 2012-10-16 Completed Date: 2012-12-26 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L692-702 Citation Subset: IM |
Affiliation:
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Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actin Cytoskeleton
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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:
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HL085324/HL/NHLBI NIH HHS; HL095451/HL/NHLBI NIH HHS; K08 HL094666/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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; 55520-40-6/Tyrosine; 9007-34-5/Collagen; EC 2.7.10.2/Focal Adhesion Kinase 1; EC 2.7.10.2/Ptk2 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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