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Updated: Aug 21, 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

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Caveolae are negative regulators of transforming growth factor-beta1 signaling in ureteral smooth muscle cells

Maximilian Stehr1, Carlos R Estrada, Joseph Khoury

  • 1Department of Urology (Urological Diseases Research Center), Children's Hospital Boston, Massachusetts 02115, USA.

The Journal of Urology
|November 13, 2004
PubMed
Abstract

Insights

Transforming growth factor-beta1 (TGF-beta1) inhibits ureteral smooth muscle cell growth. Disrupting caveolae enhances TGF-beta1

Area of Science:

  • Urology
  • Cell Biology
  • Biochemistry

Background:

  • Lipid rafts/caveolae regulate ureteral smooth muscle cell (USMC) growth signals.
  • Mechanisms of ureteral cell regulation are not fully understood.

Purpose of the Study:

  • To investigate if caveolae regulate growth inhibitory signaling by transforming growth factor-beta1 (TGF-beta1) in USMCs.
  • To determine the role of caveolae in TGF-beta1 mediated growth inhibition.

Main Methods:

  • Assessed TGF-beta1 signaling components (receptors, Smad-2) in USMCs via immunoblot and mRNA analysis.
  • Measured TGF-beta1's effect on DNA synthesis using H-thymidine incorporation.
  • Disrupted caveolae using cholesterol depletion/replenishment and evaluated TGF-beta1-responsive gene expression with a 3TP-Lux reporter construct.

Main Results:

  • USMCs express TGF-beta1 signaling pathway components.
  • TGF-beta1 potently inhibited USMC DNA synthesis.
  • Caveolae disruption enhanced TGF-beta1's inhibitory effect on DNA synthesis and stimulated gene activity, effects reversible upon cholesterol restoration.

Conclusions:

  • TGF-beta1 is a potent USMC growth inhibitor.
  • Caveolae ablation enhances TGF-beta1 signaling, suggesting caveolae negatively regulate this pathway.
  • Findings implicate TGF-beta1 and caveolae in ureteral growth regulation and potential pathologies like smooth muscle dysplasia.

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