TY - JOUR
T1 - Angiotensin II induces apoptosis in rat glomerular epithelial cells
AU - Ding, Guohua
AU - Reddy, Krishna
AU - Kapasi, Aditi A.
AU - Franki, Nicholas
AU - Gibbons, Nora
AU - Kasinath, Balakuntalam S.
AU - Singhal, Pravin C.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - 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 I 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)-β1 production as measured by ELISA. GECs exposed to TGF-β1 demonstrated a dose- and time-dependent increase in apoptosis. ANG II-induced apoptosis was significantly inhibited by addition of anti-TGF-β1 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-β1 expression that may, importantly, contribute to the pathogenesis of glomerulosclerosis.
AB - 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 I 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)-β1 production as measured by ELISA. GECs exposed to TGF-β1 demonstrated a dose- and time-dependent increase in apoptosis. ANG II-induced apoptosis was significantly inhibited by addition of anti-TGF-β1 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-β1 expression that may, importantly, contribute to the pathogenesis of glomerulosclerosis.
KW - Angiotensin II
KW - Apoptosis
KW - Glomerular epithelial cells
KW - Glomerulosclerosis
KW - Transforming growth factor-β
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U2 - 10.1152/ajprenal.00240.2001
DO - 10.1152/ajprenal.00240.2001
M3 - Article
C2 - 12060599
AN - SCOPUS:0036089691
VL - 283
SP - F173-F180
JO - American journal of physiology. Renal physiology
JF - American journal of physiology. Renal physiology
SN - 0363-6127
IS - 1 52-1
ER -