Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cells

作者：Rogel Micah R; Soni Pritin N; Troken James R; Sitikov Albert; Trejo Humberto E; Ridge Karen M^*

来源：The FASEB Journal, 2011, 25(11): 3873-3883.

DOI：10.1096/fj.10-170795

• TGF-beta 1
• migration
• scratch wound assay
• intermediate filaments
• lung injury

The physiological and pathophysiological implications of the expression of vimentin, a type III intermediate filament protein, in alveolar epithelial cells (AECs) are unknown. We provide data demonstrating that vimentin is regulated by TGF beta 1, a major cytokine released in response to acute lung injury and that vimentin is required for wound repair and remodeling of the alveolar epithelium. Quantitative real-time PCR shows a 16-fold induction of vimentin mRNA in TGF beta 1-treated transformed AECs. Luciferase assays identify a Smad-binding element in the 5' promoter of vimentin responsible for TGF beta 1-induced transcription. Notably, TGF beta 1 induces vimentin protein expression in AECs, which is associated with a 2.5-fold increase in cell motility, resulting in increased rates of migration and wound closure. These effects are independent of cell proliferation. TGF beta 1-mediated vimentin protein expression, cell migration, and wound closure are prevented by a pharmacological inhibitor of the Smad pathway and by expression of Ad-shRNA against vimentin. Conversely, overexpression of mEmerald-vimentin is sufficient for increased cell-migration and wound-closure rates. These results demonstrate that vimentin is required and sufficient for increased wound repair in an in vitro model of lung injury.-Rogel, M. R., Soni, P. N., Troken, J. R., Sitikov, A., Trejo, H. E., Ridge, K. M. Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cells. FASEB J. 25, 3873-3883 (2011). www.fasebj.org

• 出版日期2011-11
• 单位西北大学