PI3K/Akt signaling pathway regulates autophagy induced by acute kid-ney injury in septic rats
10.3969/j.issn.1000-4718.2014.06.016
- VernacularTitle:PI3 K／Akt 信号通路在脓毒症肾脏损伤诱导的自噬中的调节作用
- Author:
Jingfen XIANG
;
Xiang YANG
;
Jianfeng GONG
;
Weijian LEI
;
Yanqiong DENG
;
Dan MU
;
Guoquan ZHONG
;
Qiyong MENG
- Publication Type:Journal Article
- Keywords:
Autophagy;
PI3K/Akt pathway;
Sepsis;
Kidney injury
- From:
Chinese Journal of Pathophysiology
2014;(6):1052-1058
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the autophagy induced by sepsis and acute kidney injury , and the regulation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in this process.METHODS: The rats were subjected to cecal ligation and puncture ( CLP) or sham operation .Histopathologic changes of the renal tissues were examined by HE staining .Blood urea nitrogen ( BUN) and serum creatinine ( SCr) were measured by chemical colorime-try.The protein expression of microtubule-associated protein light chain 3 I/II (LC3 I/II), beclin-1 and p-Akt at different time points after CLP was detected by Western blotting .In vitro, human proximal tubular epithelial cell line HK-2 were treated with LPS to induce autophagy .The protein expression of LC 3 I/II and p-Akt in the HK-2 cells after LPS treatment at different time points and different concentrations was detected by Western blotting .These molecules in HK-2 cells and apoptosis of HK-2 cells treated with LPS plus PI3K inhibitor or Akt inhibitor were also detected .RESULTS: Compared with sham group , the severe changes of renal histopathological injuries in CLP groups were observed , the levels of BUN and SCr in CLP groups were significantly increased .LC3 I/II, beclin-1 and phosphorylation of Akt gradually increased after CLP.After treatment with LPS, the expression of p-Akt (308) in the HK-2 cells gradually increased in a dose-and time-dependent fashion.The expression of beclin-1 and p-Akt (472) reached a peak at 8 h or 10 mg/L LPS treatment.Treat-ment with PI3K or Akt inhibitor down-regulated the expression of LC3 and promoted the apoptosis of HK-2 cells.CON-CLUSION:Autophagy in the kidney is induced by sepsis and acute kidney injury .PI3/Akt signaling pathway may be in-volved in this process .
