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 growt h factor (bFGF), transforming growth factor beta 1 (TGF beta 1), fetal calf serum (FCS) and angiotensin II (AngII) on cell proliferation, (H-3-thymidi ne 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 markedl y increased cell proliferation, whereas AngII increased slightly 3H-thymidi ne 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 trans cription rate. In contrast, IGF-1 and AngII, increased about 4-fold AT(2) r eceptor number, but only IGF-1 increased AT(2) mRNA. When added together th e effects of IGF-1 and AngII were more than additive on AT(2) receptor numb er, 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, posit ively or negatively, AT(2) transcription rate, whereas AngII regulates the translation rate of AT:! mRNA; 3/ all the effects of AngII on R3T3 are medi ated by AT(2) receptors since they are mimicked by the AT(2) agonist CGP421 12 and blocked by the AT(2) antagonist PD 123177.