Regulation of cell proliferation and angiotensin II type 2 receptors in R3T3 cells.

The effects of insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF), transforming growth factor beta1 (TGFbeta1), fetal calf serum (FCS) and angiotensin II (AngII) on cell proliferation, (3H-thymidine incorporation and cell number) and AT2 receptor number and mRNA levels in R3T3 cells have been studied. All growth factors as well as FCS markedly increased cell proliferation, whereas AngII increased slightly 3H-thymidine incorporation, but not cell number. TGFbeta1, bFGF and FCS reduced by more than 80% both AT2 receptor number and mRNA, by inhibiting the transcription rate. In contrast, IGF-1 and AngII increased about 4-fold AT2 receptor number, but only IGF-1 increased AT2 mRNA. When added together the effects of IGF-1 and AngII were more than additive on AT2 receptor number, but not on mRNA level. None of the factors studied modified AT2 mRNA half-life. In conclusion, the present results demonstrated that: 1/ cell proliferation is not correlated with AT2 expression; 2/ growth factors regulate, positively or negatively, AT2 transcription rate, whereas AngII regulates the translation rate of AT2 mRNA; 3/ all the effects of AngII on R3T3 are mediated by AT2 receptors since they are mimicked by the AT2 agonist CGP42112 and blocked by the AT2 antagonist PD123177.