Open AccessAll‐ trans retinoic acid inhibited angiotensin II‐induced increase in cell growth and collagen secretion of neonatal cardiac fibroblasts 1
Author(s) -
HE Yan,
HUANG Ying,
ZHOU Li,
LU Limin,
ZHU Yichun,
YAO Tai
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00296.x
Subject(s) - losartan , retinoic acid , endocrinology , medicine , angiotensin ii , secretion , transforming growth factor , receptor , cardiac fibrosis , chemistry , cell growth , angiotensin ii receptor type 1 , biology , biochemistry , fibrosis , gene
Aim: To determine whether all‐trans retinoic acid (atRA) acts to modulate angiotensin II (Ang II)‐induced cardiac fibroblast cell growth and collagen secretion. Methods: Cultured neonatal rat cardiac fibroblasts (CF) were used in the experiment. A 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazoliumbromide (MTT) assay was used to detect cell growth of the CF; and immunocytochemistry and Western blotting were used to measure the production and secretion of collagen and the expression of transforming growth factor‐β 2 ; (TGF‐β 1 ) by the CF. Results: at RA (1 × 10 −7 to 1 × 10 −5 mol/L) inhibited the Ang II‐induced increase in cell growth of CF (P<0.05). Ang II stimulated the secretion of collagen types I and III by the CF. This effect was blocked by AT1 receptor antagonist losartan (1 × 10 −6 mol/L), but not by AT2 receptor antagonist PD123319 (up to 1 × 10 −6 mol/L). Exposure of CF to at RA (1 × 10 −5 mol/L) attenuated the Ang II‐induced increase in the secretion of collagen types I and III (P<0.05). at RA (1 × 10 −5 mol/L) also blocked the Ang II‐induced increase in the expression of TGF‐β 1 Conclusion: at RA inhibits the Ang II‐induced increase in cell growth and collagen secretion of neonatal rat CF. The effect of at RA is possibly mediated by lowering the TGF‐β 1 level. These observations support the notion that at RA is a potential candidate for the prevention and therapy of cardiac remodeling.