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Updated: Jun 14, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Notch and transforming growth factor-beta (TGFbeta) signaling pathways cooperatively regulate vascular smooth muscle

Yuefeng Tang1, Sumithra Urs, Joshua Boucher

  • 1Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.

The Journal of Biological Chemistry
|April 7, 2010
PubMed

Insights

Transforming growth factor-beta (TGFbeta) and Notch signaling pathways cooperatively enhance smooth muscle cell (SMC) contractile gene expression by co-regulating Smad activity at key promoters.

Area of Science:

  • Vascular biology
  • Molecular cell biology
  • Biochemistry

Background:

  • Notch and TGFbeta signaling are crucial in vascular development and disease.
  • The molecular interplay between Notch and TGFbeta in smooth muscle cells (SMCs) remains incompletely understood.
  • Understanding this cross-talk is vital for addressing vascular pathologies.

Purpose of the Study:

  • To investigate the molecular mechanisms of cross-talk between TGFbeta1 and Notch signaling pathways.
  • To determine how this interaction influences contractile gene expression in primary human SMCs.
  • To elucidate the role of Smad proteins in mediating the cooperative effects of Notch and TGFbeta1.

Main Methods:

  • Primary human aortic smooth muscle cells were treated with TGFbeta1 and Notch activators (Notch intracellular domain or Jagged1).
  • Expression levels of SMC contractile markers (SM actin, calponin1, SM22alpha) and Notch downstream effectors were analyzed.
  • Co-immunoprecipitation assays were used to examine protein-protein interactions between Notch components, Smad proteins, and CBF1.
  • Reporter assays assessed the synergistic activation of TGFbeta-responsive promoters.

Main Results:

  • Both TGFbeta1 and Notch signaling independently induced SMC contractile markers.
  • Notch and TGFbeta1 synergistically activated SMC marker gene expression and protein levels.
  • CBF1 was found to co-immunoprecipitate with phosphoSmad2/3, linking Notch signaling to Smad activity.
  • Cooperative activation involved enhanced phosphoSmad2/3 binding to Smad consensus sites on SMC promoters.

Conclusions:

  • Notch and TGFbeta1 signaling pathways coordinately regulate SMC contractile phenotype through parallel signaling axes.
  • The interaction between Notch and TGFbeta1 leads to synergistic activation of SMC contractile genes.
  • This co-regulation mechanism involves the modulation of Smad activity at specific gene promoters, offering insights into vascular cell function and disease.

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