Angiotensin II induces apoptosis in rat glomerular epithelial cells
Angiotensin II induces apoptosis in rat glomerular epithelial cells
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DOI：
10.1152/ajprenal.00240.2001
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发表时间：
2002-07-01
影响因子：
4.2
通讯作者：
Singhal, PC
中科院分区：
文献类型：
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作者：
Ding, GH;Reddy, K;Singhal, PC
ANG II已被证明可调节肾细胞生长，并有助于肾小球硬化的病理生物学。肾小球内脏上皮细胞（GEC）的损伤或缺失被认为在肾小球硬化的发生和发展中起着关键作用。在本研究中，我们研究了血管紧张素II对GEC凋亡的影响。将大鼠GEC与增加剂量的ANG II孵育可变的时间段。细胞核染色和DNA片段化分析检测细胞凋亡。ANG Ⅱ诱导GEC凋亡呈剂量和时间依赖性. ANG II受体1型拮抗剂氯沙坦或ANG II受体2型拮抗剂PD-123319可减弱促凋亡作用，并可通过与联合拮抗剂孵育完全阻断。此外，ANG II刺激转化生长因子（TGF）-β 1的产生，如ELISA所测量。暴露于TGF-β 1的GECs表现出凋亡的剂量和时间依赖性增加。ANG II诱导的细胞凋亡被加入抗TGF-β 1抗体显著抑制。ANG Ⅱ还可上调GECs中Fas、FasL和Bax的表达，下调Bcl-2的表达。这些研究表明，血管紧张素II诱导GEC凋亡的机制，涉及TGF-β 1的表达，可能是重要的，有助于肾小球硬化症的发病机制。
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.