Effect of Complement C5a/C5aR pathway on autophagy induced by renal ischemia-reperfusion injury

Kun Zhang; You LI; Ming Tang; Quanyou Zheng; Keqin Zhang

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Effect of Complement C5a/C5aR pathway on autophagy induced by renal ischemia-reperfusion injury

VernacularTitle:补体C5a/C5aR通路对小鼠肾缺血再灌注损伤引发自噬的影响
Author: Kun ZHANG ; You LI ; Ming TANG ; Quanyou ZHENG ; Keqin ZHANG
Keywords: Renal ischemia-reperfusion injury; Complement C5a/C5aR; Autophagy
From: Chinese Journal of Organ Transplantation 2016;37(10):620-626
CountryChina
Language:Chinese
Abstract: Objective To investigate the expression of autophagy and the effect of complement C5a/C5aR pathway on autophagy induced by renal ischemia reperfusion injury (IRI).Methods MaleWT and C5aR gene knockout (BALB/C background) mice were selected.The model of renal IRI was established by occluding bilateral renal pedicles with microaneurysm clamps.Mice were divided into wild type BALB/C (WT) group and C5aR gene knock out (C5aRKO) group.The pathology of kidney was assessed by HE staining.The levels of BUN and KIM-1 were detected 24 h after reperfusion.The expression of the autophagy-associated protein (LC3 Ⅱ/LC3 Ⅰ and P62) was measured by Western blotting and immunofluorescence.In vitro,human renal tubular epithelial cells (HK2) were cultured.The expression of LC3 in HK2 cells was investigated by immunofluorescence and Western blotting after being treated with recombinant C5a or C5a combined with C5aR antagonist (C5aRA).Results As compared with WT group,the severity of kidney injury was obviously reduced in C5aRKO group (P＜0.05).After ischemia-reperfusion,the expression of autophagy-related protein LC3 gradually increased with the reperfusion time prolonged.The level of autophagy induced by ischemia-reperfusion was significantly reduced in C5aRKO group as compared with WT group (P＜0.05).In addition,the expression of autophagy-related protein LC3 Ⅱ in HK2 cells was increased with the augment of C5a stimulation concentration in vitro.Blockage of C5aR pathway by C5aRA led to a significant decrease in autophagy (P ＜ 0.05).Conclusion Complement C5a/C5aR pathway promotes renal IRI-induced autophagy.