Journal
FASEB JOURNAL
Volume 25, Issue 11, Pages 3873-3883Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.10-170795
Keywords
TGF-beta 1; migration; scratch wound assay; intermediate filaments; lung injury
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Funding
- U.S. National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NIH-NHLBI) [PO1 HL71643, T32-076139-02]
- Department of Veterans Affairs
- American Heart Association (AHA) [10PRE4210064]
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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
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