Format

Send to:

Choose Destination
See comment in PubMed Commons below
Hypertension. 2001 Aug;38(2):261-6.

Nitric oxide attenuates the expression of transforming growth factor-beta(3) mRNA in rat cardiac fibroblasts via destabilization.

Author information

  • 1Université de Montréal, Departemént de Physiologie, et l'Institut de Cardiologie de Montréal, Montréal, Québec, Canada.

Abstract

Transforming growth factor-beta (TGF-beta) has been implicated in the development of interstitial fibrosis in cardiac hypertrophy. NO has been regarded as a potent inhibitor of cardiac fibroblast growth, albeit the modulation of cellular events associated with interstitial fibrosis remains undefined. In this regard, the regulation of TGF-beta mRNA expression by the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) was examined in neonatal rat cardiac fibroblasts. SNAP treatment for 4 hours decreased TGF-beta(3) mRNA levels, an effect mimicked by 8-bromo-cGMP. TGF-beta(3) mRNA, however, had returned to levels observed in the untreated cells after a 24-hour exposure to SNAP, whereas a decreased expression persisted with 8-bromo-cGMP. In contrast to TGF-beta(3), TGF-beta(1) mRNA levels were modestly increased in response to cGMP-generating molecules. The treatment with actinomycin D for at least 8 hours did not appreciably alter TGF-beta(3) mRNA levels. By contrast, SNAP treatment caused a rapid decrease of TGF-beta(3) mRNA with a half-life of 3.3+/-0.2 hours, thereby supporting a mechanism of destabilization. The pretreatment with SNAP inhibited angiotensin II-stimulated protein synthesis and the concomitant expression of TGF-beta(3) mRNA. These data reveal a disparate pattern of TGF-beta(1) and TGF-beta(3) mRNA regulation by NO and highlight a novel mechanism of destabilization contributing to the decreased expression of TGF-beta(3) mRNA. The modulation of both basal and angiotensin II-stimulated TGF-beta(3) mRNA expression provides a mechanism by which NO may influence the progression of interstitial fibrosis.

PMID:
11509487
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk