| Autor: |
Rogel MR; Department of Biomedical Engineering, Northwestern University, Chicago, Illinois 60611, USA., Soni PN, Troken JR, Sitikov A, Trejo HE, Ridge KM |
| Jazyk: |
angličtina |
| Zdroj: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2011 Nov; Vol. 25 (11), pp. 3873-83. Date of Electronic Publication: 2011 Jul 29. |
| DOI: |
10.1096/fj.10-170795 |
| Abstrakt: |
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 TGFβ1, 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 TGFβ1-treated transformed AECs. Luciferase assays identify a Smad-binding element in the 5' promoter of vimentin responsible for TGFβ1-induced transcription. Notably, TGFβ1 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. TGFβ1-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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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