The role of glucocorticoid receptor in ischemia-reperfusion-induced kidney injury

doi:10.3969/j.issn.1006-7795.2022.02.017

Abstract

Abstract: Objective To investigate the changes and role of glucocorticoid receptor(GR) in ischemia-reperfusion(IR)-induced kidney injury. Methods The left renal pedicle of the mouse was clamped for 45 minutes with a microvascular clip to induce kidney injury.The blood urea nitrogen (BUN) and serum creatinine (Scr) levels were detected with the BUN and Scr kits on the 5th,15th,30th and 80th day. Periodic acid-Schiff (PAS) staining and hematoxylin-eosin (HE) staining were used to measure the inflammatory cells infiltration of renal tissues.The expression levels of kidney injury molecular-1 (Kim-1), inflammatory cell markers F4/80 and CD3 were disclosed by immunofluorescence (IF). The mRNA level of GR was detected with real time quantitative PCR (RT-qPCR), and its protein level was measured with IF and Western blotting(WB) technology. After intraperitoneal injection of mifepristone (MF, 50 mg·kg^-1·d^-1) in IR-induced 8 weeks female mice, the levels of BUN and Scr in the experimental group and the control group were measured, and the expression of Kim-1 and F4/80 were detected with IF. Results BUN and Scr level of the IR group was 4.9 and 8.3 times higher than that of the sham group in 5th day after IR.The mRNA level of inflammatory cells markers in the IR group was 3-5 times higher, respectively, than those of the sham group, and the mRNA level of GR was 3.5 times lower than those of the sham group. The protein level of GR also dropped significantly. At the same time of IR treatment, after injection of MF to block GR, BUN and Scr were increased compared with the control group, indicating that blocking GR would lead to aggravated renal function damage after IR. The expression levels of Kim-1 and F4/80 in the experimental group were prominently upregulated, which indicated that when GR was blocked,the inflammatory response was enhanced and the kidney injury was aggravated. Conclusion This study revealed that there was a significant correlation between the expression of GR and the degree of renal injury in IR induced renal injury and blocking GR could aggravate IR-induced renal injury.

Key words: kidney injury, glucocorticoid receptor(GR), ischemia-reperfusion(IR), inflammatory response, mifepristone

CLC Number:

Wang Xiangdong, Jiang Min, Wang Xin, Gong Yongfeng. The role of glucocorticoid receptor in ischemia-reperfusion-induced kidney injury[J]. Journal of Capital Medical University, 2022, 43(2): 260-268.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2022.02.017

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2022/V43/I2/260

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