Angiotensin II induced apoptosis in rat glomerular epithelial cells in a dose- and time-dependent manner, mediated by TGF-beta1 expression.
Does Angiotensin II induce apoptosis in rat glomerular epithelial cells?
Angiotensin II induces apoptosis in glomerular epithelial cells via a TGF-beta1-dependent mechanism, suggesting a cellular pathway for its role in the pathogenesis of glomerulosclerosis.
ANG II has been shown to modulate kidney cell growth and contribute to the pathobiology of glomerulosclerosis. Glomerular visceral epithelial cell (GEC) injury or loss is considered to play a pivotal role in the initiation and progression of glomerulosclerosis. In the present study, we investigated the effect of ANG II on GEC apoptosis. Rat GECs were incubated with increasing doses of ANG II for variable time periods. Apoptosis was evaluated by cell nucleus staining and DNA fragmentation assay. ANG II induced GEC apoptosis in a dose- and time-dependent manner. The proapoptotic effect was attenuated by the ANG II receptor type 1 antagonist losartan or the ANG II receptor type 2 antagonist PD-123319 and was completely blocked by incubation with the combined antagonists. Moreover, ANG II stimulated transforming growth factor (TGF)-beta1 production as measured by ELISA. GECs exposed to TGF-beta1 demonstrated a dose- and time-dependent increase in apoptosis. ANG II-induced apoptosis was significantly inhibited by addition of anti-TGF-beta1 antibody. ANG II also upregulated the expression of Fas, FasL, and Bax and downregulated the expression of Bcl-2 in GECs. These studies suggest that ANG II induces GEC apoptosis by a mechanism involving TGF-beta1 expression that may, importantly, contribute to the pathogenesis of glomerulosclerosis.
Ding et al. (Mon,) conducted a other in Glomerulosclerosis. Angiotensin II was evaluated on GEC apoptosis. Angiotensin II induced apoptosis in rat glomerular epithelial cells in a dose- and time-dependent manner, mediated by TGF-beta1 expression.