ALK5 and Smad4 are involved in TGF-β1-induced pulmonary endothelial permeability

Anna A. Birukova, Djanibek Adyshev, Boris Gorshkov, Konstantin G. Birukov, Alexander D. Verin

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The ability of inflammatory cytokine TGF-β1 to alter endothelial cell phenotype suggests its role in the regulation of vascular endothelial cell permeability. We demonstrate that depletion of TGF-β1 receptor ALK5 and regulatory protein Smad4, but not ALK1 receptor attenuates TGF-β1-induced permeability increase and significantly inhibits TGF-β1-induced EC contraction manifested by actin stress fiber formation and increased MLC and MYPT1 phosphorylation. Consistent with these results, EC treatment with SB 431542, an inhibitor of ALK5 but not ALK1 receptor, significantly attenuates TGF-β1-induced permeability. Thus, our data demonstrate for the first time direct link between TGF-β1-mediated activation of ALK5/Smad and EC barrier dysfunction.

Original languageEnglish (US)
Pages (from-to)4031-4037
Number of pages7
JournalFEBS Letters
Volume579
Issue number18
DOIs
StatePublished - Jul 18 2005

Fingerprint

Endothelial cells
Permeability
Smad4 Protein
Lung
Phosphorylation
Endothelial Cells
Actins
Stress Fibers
Chemical activation
Cytokines
Fibers
Phenotype
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide

Keywords

  • ALK1 and 5
  • Actin
  • Permeability
  • Pulmonary endothelium
  • Smad4
  • TGFβ1

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

ALK5 and Smad4 are involved in TGF-β1-induced pulmonary endothelial permeability. / Birukova, Anna A.; Adyshev, Djanibek; Gorshkov, Boris; Birukov, Konstantin G.; Verin, Alexander D.

In: FEBS Letters, Vol. 579, No. 18, 18.07.2005, p. 4031-4037.

Research output: Contribution to journalArticle

Birukova, Anna A. ; Adyshev, Djanibek ; Gorshkov, Boris ; Birukov, Konstantin G. ; Verin, Alexander D. / ALK5 and Smad4 are involved in TGF-β1-induced pulmonary endothelial permeability. In: FEBS Letters. 2005 ; Vol. 579, No. 18. pp. 4031-4037.
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AU - Verin, Alexander D.

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