title: Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cells.
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.
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Micah R
authors.initials: MR
authors.lastname: Rogel
authors.forename: Pritin N
authors.initials: PN
authors.lastname: Soni
authors.forename: James R
authors.initials: JR
authors.lastname: Troken
authors.forename: Albert
authors.initials: A
authors.lastname: Sitikov
authors.forename: Humberto E
authors.initials: HE
authors.lastname: Trejo
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ridge
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D051785:Smad Proteins / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014746:Vimentin / Q000096:biosynthesis / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D051785:Smad Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014746:Vimentin