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

Micah R. Rogel, Pritin N. Soni, James R. Troken, Albert Sitikov, Humberto E. Trejo, Karen M. Ridge*

*Corresponding author for this work

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3873-3883
Number of pages11
JournalFASEB Journal
Volume25
Issue number11
DOIs
Publication statusPublished - Nov 1 2011

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Keywords

  • Intermediate filaments
  • Lung injury
  • Migration
  • Scratch wound assay
  • TGF-β1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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