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RGS2 is a negative regulator of Gq/11‐mediated signaling and cell proliferation in adult rat ventricular fibroblasts
Author(s) -
Zhang Peng,
King Michelle,
Ayrapetov Marina,
Mende Ulrike
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.588.2
Subject(s) - rgs2 , regulator of g protein signaling , gq alpha subunit , g protein , angiotensin ii , microbiology and biotechnology , signal transduction , biology , receptor , regulator , stimulation , medicine , endocrinology , g protein coupled receptor , chemistry , gtpase activating protein , gene , biochemistry
Cardiac fibroblasts (CF) contribute to cardiac remodeling by assuming an “activated” myofibroblast (MyoFb) phenotype. Many G protein‐coupled receptors are involved in CF activation. G proteins are controlled by Regulators of G protein Signaling (RGS). RGS expression and function in CF and MyoFb are unknown. We set out to identify which RGS are expressed in isolated adult rat ventricular CF (passage P0‐P2) and to begin to delineate their function. Morphologic changes and expression of MyoFb markers (e.g., α‐smooth muscle actin) indicated gradual conversion from CF (P0) to MyoFb (P2). We detected mRNA of 14 RGS by RT‐PCR that were differentially regulated during CF to MyoFb conversion. Only RGS2 mRNA was markedly up‐regulated in response to short‐term stimulation of G q/11 ‐coupled Angiotensin II (Ang II) and G s ‐coupled β‐adrenergic receptors. Adenoviral RGS2 expression blunted Ang II‐induced phospholipase C β activation by 65±2% (P0), 66±2% (P1) and 78±3% (P2) (n=3, P<0.05) and CF proliferation (BrdU incorporation) by 37±5% (n=10, P<0.05). RGS2 had no effect on G s ‐coupled cAMP accumulation. Thus, while RGS2 is selectively up‐regulated in response to G q/11 and G s activation, it negatively regulates only G q/11 ‐mediated signaling and proliferation in both CF and MyoFb. These data point to RGS2 as an important regulator of CF and MyoFb signaling and function. Supported by the NIH and American Heart Association.