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The molecular mechanism involved is not fully understood. Neuronal Wiskott\u2010Aldrich syndrome protein (N\u2010WASP) has an essential role in actin structure dynamics. We hypothesized that N\u2010WASP plays a critical role in these TGF\u2010\u03b21\u2010induced responses. In these cell monolayers, we demonstrated that N\u2010WASP down\u2010regulation by short hairpin RNA prevented TGF\u2010\u03b21\u2010mediated disruption of the cortical actin structure, actin stress filament formation, and increased permeability. Furthermore, N\u2010WASP down\u2010regulation blocked TGF\u2010\u03b21 activation mediated by IL\u20101\u03b2 in alveolar epithelial cells, which requires actin stress fiber formation. Control short hairpin RNA had no effect on these TGF\u2010\u03b21\u2010induced responses. TGF\u2010\u03b21\u2010induced phosphorylation of Y256 of N\u2010WASP\n                    <jats:italic>via<\/jats:italic>\n                    activation of small Rho GTPase and focal adhesion kinase mediates TGF\u2010\u03b21\u2010induced paracellular permeability and actin cytoskeleton dynamics.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , compared with controls, N\u2010WASP down\u2010regulation increases survival and prevents lung edema in mice induced by bleomycin exposure\u2014a lung injury model in which TGF\u2010\u03b21 plays a critical role. Our data indicate that N\u2010WASP plays a crucial role in the development of TGF\u2010\u03b21\u2010mediated acute lung injury by promoting pulmonary edema\n                    <jats:italic>via<\/jats:italic>\n                    regulation of actin cytoskeleton dynamics.\u2014Wagener, B. M., Hu, M., Zheng, A., Zhao, X., Che, P., Brandon, A., Anjum, N., Snapper, S., Creighton, J., Guan, J.\u2010L., Han, Q., Cai, G.\u2010Q., Han, X., Pittet, J.\u2010F., Ding, Q. Neuronal Wiskott\u2010Aldrich syndrome protein regulates TGF\u2010\u03b21\u2010mediated lung vascular permeability. FASEB J. 30, 2557\u20102569 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201600102r","type":"journal-article","created":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T22:13:54Z","timestamp":1459289634000},"page":"2557-2569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Neuronal Wiskott\u2010Aldrich syndrome protein regulates TGF\u2010\u03b21\u2010mediated lung vascular permeability"],"prefix":"10.1096","volume":"30","author":[{"given":"Brant M.","family":"Wagener","sequence":"first","affiliation":[{"name":"Division of Critical Care University of Alabama at Birmingham Birmingham Alabama USA"},{"name":"Division of Molecular and Translational Biomedicine Department of Anesthesiology and Perioperative Medicine University of Alabama at Birmingham 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