Angiotensin II induces apoptosis in rat glomerular epithelial cells

Guohua Ding, Krishna Reddy, Aditi A. Kapasi, Nicholas Franki, Nora Gibbons, Balakuntalam S. Kasinath, Pravin C. Singhal

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145 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F173-F180
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number1 52-1
StatePublished - Jul 4 2002

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Keywords

  • Angiotensin II
  • Apoptosis
  • Glomerular epithelial cells
  • Glomerulosclerosis
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Ding, G., Reddy, K., Kapasi, A. A., Franki, N., Gibbons, N., Kasinath, B. S., & Singhal, P. C. (2002). Angiotensin II induces apoptosis in rat glomerular epithelial cells. American Journal of Physiology - Renal Physiology, 283(1 52-1), F173-F180.