GENETIC DELETION OF AT2 RECEPTOR ANTAGONIZES ANGIOTENSIN-II-INDUCED APOPTOSIS IN FIBROBLASTS OF THE MOUSE EMBRYO

To examine whether angiotensin II (Ang II) can trigger apoptosis via A ng II type 2 (AT2) receptor, two genotypes of skin fibroblasts culture d from the AT2 receptor gene targeting homozygous (AT2-/-) and wild-ty pe (AT2+/+) mouse embryos, respectively, were studied when exposed to Ang II. In the AT2+/+ fibroblasts, mRNA expression of the AT2 receptor was modulated by Ang II in a dose-dependent manner and apoptosis appe ared with the convincing features of internucleosomal DNA fragmentatio n and DNA content decrease after stimulation with Ang II, whereas Ang II had no significant impact on the AT2-/- fibroblasts due to the AT2 receptor gene deletion. This is the first report using a gene targetin g study to demonstrate that Ang II induces apoptosis through the AT2 r eceptor in the fibroblasts of the mouse embryo. (C) 1998 Academic Pres s.