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 beta 1 (TGF beta 1), fetal calf serum (FCS) and angiotensin II (AngII) on cell proliferation, (H-3-thymidine incorporation and cell number) and AT(2) 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. TGF beta 1, bFGF and FCS reduced by more than 80 % both AT(2) receptor number and mRNA, by inhibiting the transcription rate. In contrast, IGF-1 and AngII, increased about 4-fold AT(2) receptor number, but only IGF-1 increased AT(2) mRNA. When added together the effects of IGF-1 and AngII were more than additive on AT(2) receptor number, but not on mRNA level. None of the factors studied modified AT(2) mRNA half-life. In conclusion, the present results demonstrated that: 1/ cell proliferation is not correlated with AT(2) expression; 2/ growth factors regulate, positively or negatively, AT(2) transcription rate, whereas AngII regulates the translation rate of AT:! mRNA; 3/ all the effects of AngII on R3T3 are mediated by AT(2) receptors since they are mimicked by the AT(2) agonist CGP42112 and blocked by the AT(2) antagonist PD 123177.