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

• DOI: 10.1038/s41419-021-03508-y
• Publication Date: 2021-02-26T12:04:10Z
• Authors: Zhiya Deng; Maomao Sun; Jie Wu; Haihong Fang; Shumin Cai; Sheng An; Qiaobing Huang; Zhenfeng Chen; Chenglun Wu; Ziwei Zhou; Haoran Hu; Zhenhua Zeng
• Keywords: Male; Time Factors; Enzyme Activators; Article; Cell Line; Kidney Tubules, Proximal; 03 medical and health sciences; Glucosides; Sirtuin 1; Sepsis; Stilbenes; Autophagy; Animals; Humans; 0303 health sciences; QH573-671; Acetylation; Acute Kidney Injury; 3. Good health; Enzyme Activation; Mice, Inbred C57BL; Disease Models, Animal; Resveratrol; Beclin-1; Cytology; Signal Transduction

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 is related to autophagy induction underlying mechanism this also unknown. In present study, caecal ligation puncture (CLP)-induced mice, an LPS-challenged HK-2 cell line were established mimic SAKI animal model model, respectively. results demonstrated activation promoted attenuated SAKI. deacetylated only Beclin1 but not other SIRT1-induced its protective against mediated by deacetylation at K430 K437. Moreover, two activators, resveratrol polydatin, CLP-induced septic mice. study was first demonstrate important role These findings suggest pharmacologic via SIRT1-mediated may be promising therapeutic approach for future treatment.