SIRT1 attenuates sepsis-induced acute kidney injury via Beclin1 deacetylation-mediated autophagy activation

被引：143

作者：

Deng, Zhiya ^{[1
,2
]}

Sun, Maomao ^{[1
,2
]}

Wu, Jie ^{[1
,2
]}

Fang, Haihong ^{[3
]}

Cai, Shumin ^{[1
]}

An, Sheng ^{[1
,2
]}

Huang, Qiaobing ^{[2
]}

Chen, Zhenfeng ^{[2
]}

Wu, Chenglun ^{[1
]}

Zhou, Ziwei ^{[1
]}

Hu, Haoran ^{[1
]}

Zeng, Zhenhua ^{[1
,2
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China

[2] Southern Med Univ, Sch Basic Med Sci, Guangdong Prov Key Lab Shock & Microcirculat, Guangzhou 510515, Guangdong, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Anesthesiol, Guangzhou 510515, Guangdong, Peoples R China

来源：

CELL DEATH & DISEASE | 2021年 / 12卷 / 02期

基金：

中国国家自然科学基金;

关键词：

D O I：

10.1038/s41419-021-03508-y

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Our previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.

引用

页数：13

共 35 条

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