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Nitric oxide and carbon monoxide antagonize TGF-beta through ligand-independent internalization of TbetaR1/ALK5.

Authors: Hovater, MB  Ying, WZ  Agarwal, A  Sanders, PW 
Citation: Hovater MB, etal., Am J Physiol Renal Physiol. 2014 Sep 15;307(6):F727-35. doi: 10.1152/ajprenal.00353.2014. Epub 2014 Aug 6.
Pubmed: (View Article at PubMed) PMID:25100282
DOI: Full-text: DOI:10.1152/ajprenal.00353.2014

Transforming growth factor (TGF)-beta plays a central role in vascular homeostasis and in the pathology of vascular disease. There is a growing appreciation for the role of nitric oxide (NO) and carbon monoxide (CO) as highly diffusible, bioactive signaling molecules in the vasculature. We hypothesized that both NO and CO increase endocytosis of TGF-beta receptor type 1 (TbetaR1) in vascular smooth muscle cells (VSMCs) through activation of dynamin-2, shielding cells from the effects of circulating TGF-beta. In this study, primary cultures of VSMCs from Sprague-Dawley rats were treated with NO-releasing molecule 3 (a NO chemical donor), CO-releasing molecule 2 (a CO chemical donor), or control. NO and CO stimulated dynamin-2 activation in VSMCs. NO and CO promoted time- and dose-dependent endocytosis of TbetaR1. By decreasing TbetaR1 surface expression through this dynamin-2-dependent process, NO and CO diminished the effects of TGF-beta on VSMCs. These findings help explain an important mechanism by which NO and CO signal in the vasculature by decreasing surface expression of TbetaR1 and the cellular response to TGF-beta.

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CRRD Object Information
CRRD ID: 9685289
Created: 2014-12-31
Species: All species
Last Modified: 2014-12-31
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.