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Nitric oxide and carbon monoxide antagonize TGF-β through ligand-independent internalization of TβR1/ALK5

Michael B Hovater1, Wei-Zhong Ying1, Anupam Agarwal2

  • 1Department of Medicine University of Alabama at Birmingham, Birmingham, Alabama;

American Journal of Physiology. Renal Physiology
|August 8, 2014
PubMed

Insights

Nitric oxide (NO) and carbon monoxide (CO) reduce vascular smooth muscle cell exposure to transforming growth factor-beta (TGF-β). These gases promote the internalization of the TGF-β receptor type 1 (TβR1) via dynamin-2, thereby protecting cells.

Area of Science:

  • Vascular Biology
  • Cell Signaling
  • Molecular Medicine

Background:

  • Transforming growth factor-beta (TGF-β) is crucial for vascular homeostasis and disease.
  • Nitric oxide (NO) and carbon monoxide (CO) are key signaling molecules in the vasculature.

Purpose of the Study:

  • To investigate if NO and CO increase the endocytosis of TGF-β receptor type 1 (TβR1) in vascular smooth muscle cells (VSMCs).
  • To determine if this process is mediated by dynamin-2 and protects cells from TGF-β effects.

Main Methods:

  • Primary VSMCs from Sprague-Dawley rats were treated with NO or CO chemical donors.
  • Dynamin-2 activation, TβR1 endocytosis, and surface expression were measured.
  • Cellular response to TGF-β was assessed.

Main Results:

  • NO and CO significantly stimulated dynamin-2 activation in VSMCs.
  • Both gases promoted time- and dose-dependent endocytosis of TβR1.
  • Reduced TβR1 surface expression diminished TGF-β effects on VSMCs.

Conclusions:

  • NO and CO decrease TβR1 surface expression in VSMCs through a dynamin-2-dependent endocytosis pathway.
  • This mechanism explains how NO and CO modulate cellular responses to TGF-β in the vasculature.
Keywords:
activin receptor-like kinase 5carbon monoxidedynamin-2nitric oxidetransforming growth factor-βvascular smooth muscle

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