{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:41:31Z","timestamp":1790358091054,"version":"4.1.0"},"reference-count":52,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2012,10,15]]},"abstract":"<jats:p>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 \u03b1-smooth muscle actin (\u03b1-SMA). These \u03b1-SMA-containing cytoplasmic filaments are important for myofibroblast contractility during tissue remodeling. However, the molecular mechanisms regulating the formation and maturation of \u03b1-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 \u03b1-SMA-containing cytoplasmic filaments during myofibroblast differentiation and in myofibroblast contractility. Focal adhesion kinase (FAK) is activated by transforming growth factor-\u03b21 (TGF-\u03b21) and is required for phosphorylation of tyrosine residue 256 (Y256) of N-WASP. Phosphorylation of Y256 of N-WASP is essential for TGF-\u03b21-induced formation of \u03b1-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 \u03b1-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 \u03b1-SMA-containing cytoplasmic filaments during myofibroblast differentiation and maturation.<\/jats:p>","DOI":"10.1152\/ajplung.00390.2011","type":"journal-article","created":{"date-parts":[[2012,8,12]],"date-time":"2012-08-12T02:04:13Z","timestamp":1344737053000},"page":"L692-L702","source":"Crossref","is-referenced-by-count":34,"title":["Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of \u03b1-smooth muscle actin filaments during myofibroblast differentiation"],"prefix":"10.1152","volume":"303","author":[{"given":"Guo-Qiang","family":"Cai","sequence":"first","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu-Fang","family":"Chou","sequence":"additional","affiliation":[{"name":"Biochemistry &amp; Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Hu","sequence":"additional","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni","family":"Zheng","sequence":"additional","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis F.","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Department of Physiology, UCSF, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Lin","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Fang","sequence":"additional","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy R.","family":"Luckhardt","sequence":"additional","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor J.","family":"Thannickal","sequence":"additional","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Departments of 1Medicine, Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041590120"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00666-4"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200403127"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.01.021"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.075218"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.4.887"},{"key":"B7","first-page":"21","volume":"63","author":"Darby I","year":"1990","journal-title":"Lab Invest"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1067-1927.2005.130102.x"},{"key":"B9","first-page":"103","volume":"122","author":"Desmouliere A","year":"1993","journal-title":"J Cell Biochem"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803645200"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409180200"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2165\/11591490-000000000-00000"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304685200"},{"key":"B14","first-page":"5336","volume":"62","author":"Ding Q","year":"2002","journal-title":"Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3109\/10409230903277340"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/BF02147594"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.124.4.401"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0005ED"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1385\/IR:21:2-3:293"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.9.2730"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E02-11-0729"},{"key":"B22","first-page":"657","volume":"157","author":"Hinz B","year":"2002","journal-title":"J Cell Biochem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070112"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2006.10.001"},{"key":"B25","author":"Huang X","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27183"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0243OC"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01586"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090256"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1242\/dev.035246"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2005.01192.x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80545-0"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200708-1291OC"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00373"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1378\/chest.122.6_suppl.286S"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00120-X"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80732-1"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1996.76.1.69"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200406151"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200411155"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200601-008AW"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/35010517"},{"key":"B43","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1242\/jcs.115.4.699","volume":"115","author":"Sturge J","year":"2002","journal-title":"J Cell Sci"},{"key":"B44","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1242\/jcs.114.10.1801","volume":"114","author":"Takenawa T","year":"2001","journal-title":"J Cell Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2069"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208544200"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.55.091902.103810"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01651-7"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200704042"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310739200"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511825200"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.11.003"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00390.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T10:50:10Z","timestamp":1643194210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00390.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,15]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,10,15]]}},"alternative-id":["10.1152\/ajplung.00390.2011"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00390.2011","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,15]]}}}