SIRT7 silencing by miR-152-3p confers cell apoptosis and renal functional impairment induced by renal ischaemia/reperfusion injury

被引:6
|
作者
Wang, Yan [1 ]
Wu, Xue Qing [1 ]
Cai, Jing Ran [1 ]
Ji, Huai Xue [1 ]
Xu, Tie [2 ]
机构
[1] Xuzhou Med Univ, Dept Pharm, Affiliated Hosp, Xuzhou 221002, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Emergency Ctr, Affiliated Hosp, Xuzhou 221002, Jiangsu, Peoples R China
关键词
Acute renal injury; SIRT7; miR-152-3p; Cell apoptosis; FOXO3A; EXPRESSION;
D O I
10.1007/s11255-022-03330-1
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose Acute kidney injury (AKI) induced by renal ischaemia/reperfusion (I/R) during renal transplantation has been reported to be linked to the regulation of SIRT2, one of the members of SIRTUINS family. Current work is attempted to explore the influence and mechanism of SIRT7 in renal cell apoptosis controlled by miR-152-3p during renal I/R injury. Methods Three databases were used to select the miRNAs regulating the expression of SIRT7. Overexpression and inhibition of miR-152-3p and Luciferase assay were employed to certify the modulation of miR-152-3p to SIRT7 in cells. RT-qPCR assay was used to measure the mRNA levels. Western blot assay was employed to determine the expression of proteins. TUNEL assay and Flow Cytometry were conducted to analyze cell apoptosis. Results SIRT7 expression decreased in tissues of AKI patients and rats underwent renal I/R, which was associated with enhanced impairment of renal function. SIRT7 downregulation was attributed to the direct inhibition by miR-152-3p due to binding and inhibiting its seed sequence in 3 '-UTR of SIRT7 mRNA. Consequently, the upregulation of miR-152-3p led to an inhibition of SIRT7 expression, an increase in expression of extrinsic apoptosis molecules containing FOXO3a, Bim, and caspase3, and apoptotic renal cells; while miR-152-3p inhibition abolished these phenotypes. Conclusion SIRT7 downregulation by miR-152-3p is a leading cause of renal cell apoptosis and functional impairment induced by renal I/R. Inhibition of miR-152-3p to restore SIRT7 expression can be a promising strategy against renal I/R injury.
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收藏
页码:367 / 376
页数:10
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