Caveolin-1 deficiency induces spontaneous endothelial-to-mesenchymal transition in murine pulmonary endothelial cells in vitro

Am J Pathol. 2013 Feb;182(2):325-31. doi: 10.1016/j.ajpath.2012.10.022. Epub 2012 Nov 27.


It was previously demonstrated that transforming growth factor β (TGF-β) induces endothelial-to-mesenchymal transition (EndoMT) in murine lung endothelial cells (ECs) in vitro. Owing to the important role of caveolin-1 (CAV1) in TGF-β receptor internalization and TGF-β signaling, the participation of CAV1 in the induction of EndoMT in murine lung ECs was investigated. Pulmonary ECs were isolated from wild-type and Cav1 knockout mice using immunomagnetic methods with sequential anti-CD31 and anti-CD102 antibody selection followed by in vitro culture and treatment with TGF-β1. EndoMT was assessed by semiquantitative RT-PCR for Acta2, Col1a1, Snai1, and Snai2; by immunofluorescence for α-smooth muscle actin; and by Western blot analysis for α-smooth muscle actin, SNAIL1, SNAIL2, and the α2 chain of type I collagen. The same studies were performed in Cav1(-/-) pulmonary ECs after restoration of functional CAV1 domains using a cell-permeable CAV1 scaffolding domain peptide. Pulmonary ECs from Cav1 knockout mice displayed high levels of spontaneous Acta2, Col1A, Snai1, and Snai2 expression, which increased after TGF-β treatment. Spontaneous and TGF-β1-stimulated EndoMT were abrogated by the restoration of functional CAV1 domains using a cell-permeable peptide. The findings suggest that CAV1 regulation of EndoMT may play a role in the development of fibroproliferative vasculopathies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caveolin 1 / deficiency*
  • Caveolin 1 / metabolism
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Lung / pathology*
  • Mesoderm / drug effects
  • Mesoderm / metabolism
  • Mesoderm / pathology*
  • Mice
  • Mice, Knockout
  • Peptides / chemistry
  • Peptides / pharmacology
  • Protein Structure, Tertiary
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / pharmacology


  • Caveolin 1
  • Peptides
  • Snai1 protein, mouse
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors
  • Transforming Growth Factor beta1