Mechanism of miR?21 in delayed ischemia preconditioning and its protection against subsequent ischemia reperfusion injury in kidney
10.3760/cma.j.issn.1001-7097.2015.09.007
- VernacularTitle:微RNA-21在肾缺血预处理中的保护作用及其机制
- Author:
Xiaoyan JIAO
;
Xialian XU
;
Yi FANG
;
Hui ZHANG
;
Bingying ZHANG
;
Xiaoqiang DING
;
Jie TENG
- Publication Type:Journal Article
- Keywords:
Reperfusion injury;
Hypoxia inducible factor 1;
Procollagen ? proline dioxygenase;
miR?21;
Kidney failure;
acute
- From:
Chinese Journal of Nephrology
2015;31(9):674-679
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the molecular mechanism of protection of ischemia preconditioning on renal ischemia reperfusion injury. Methods Male C57/BL6N mice were randomly divided into two groups: in IR group, 35 min ischemia was induced by occlusion of both renal pedicles followed by 24 h perfusion (I/R). 15 min ischemia was induced 4 days before I/R in IPC group. Blood sample and kidney were collected in IR and IPC group after 24 h perfusion. Serum creatinine (Scr) and histological changes were used to evaluate the renal injury. PHD2 and HIF-1αwere evaluated by Western blotting, miR-21 expression was confirmed by real-time PCR. In vitro, hypoxic model was established by 1% O2 in HK-2 cells. Knockdown of miR-21 in hypoxic model was perfermed by locked nucleic acid modified-anti-miR-21 transfection. The levels of miR-21, HIF-1α and PHD2 mRNA were confirmed by real-time PCR. The levels of HIF-1α and PHD2 proteins were tested by Western blotting. Results In vivo, Compared with IR group, the renal function and histological changes were improved in IPC group (P<0.01). Compared with IR group, the expression of miR-21(P<0.01) and HIF-1α(P<0.05) were increased in IPC group, while PHD2 was reduced (P<0.01). In vitro, hypoxia reduced miR-21. The inhibition of miR-21 could increased the expression of PHD2 (P<0.05). Conclusions Ischemia preconditioning may exert protection against renal ischemia reperfusion injury by inhibiting PHD2.
