Yu Chen1, Hao Liu2, Xueyang Zheng1, Jiyuan Wang1, Liming Wang1, Jinghui Yang1. 1. Department of Organ Transplantation, Shanghai Changzheng Hospital, Navy Medical University Shanghai, China. 2. Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai, China.
Abstract
BACKGROUND: Renal ischemia-reperfusion (IR) injury is a therapeutic challenge for surgeons. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that plays a vital role in modulating cellular senescence and aging. In this study, we determined whether SIRT1 upregulation could alleviate renal IR injury and the underlying mechanism. METHODS: A renal IR model was induced in male C57BL/6 mice. Blood urea nitrogen and serum creatinine were evaluated as markers of kidney function, and renal injury was assessed by pathological examination. The inflammatory milieu was analyzed by real-time RT-PCR and myeloperoxidase immunofluorescence assays. Western blotting was used to quantify SIRT1 protein expression, endoplasmic reticulum stress, and autophagy. RESULTS: SIRT1 was upregulated in renal tissue after IR. Blood analysis and histopathologic examination demonstrated that SIRT1 preserved renal function and reduced renal damage. Further evaluation illustrated that IR induced autophagy and endoplasmic reticulum stress, while SIRT1 upregulation reduced endoplasmic reticulum stress-mediated autophagy levels. CONCLUSIONS: SIRT1 upregulation protects the kidney against IR-induced injury by inhibiting endoplasmic reticulum stress-mediated autophagy. AJTR
BACKGROUND: Renal ischemia-reperfusion (IR) injury is a therapeutic challenge for surgeons. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that plays a vital role in modulating cellular senescence and aging. In this study, we determined whether SIRT1 upregulation could alleviate renal IR injury and the underlying mechanism. METHODS: A renal IR model was induced in male C57BL/6 mice. Blood urea nitrogen and serum creatinine were evaluated as markers of kidney function, and renal injury was assessed by pathological examination. The inflammatory milieu was analyzed by real-time RT-PCR and myeloperoxidase immunofluorescence assays. Western blotting was used to quantify SIRT1 protein expression, endoplasmic reticulum stress, and autophagy. RESULTS: SIRT1 was upregulated in renal tissue after IR. Blood analysis and histopathologic examination demonstrated that SIRT1 preserved renal function and reduced renal damage. Further evaluation illustrated that IR induced autophagy and endoplasmic reticulum stress, while SIRT1 upregulation reduced endoplasmic reticulum stress-mediated autophagy levels. CONCLUSIONS: SIRT1 upregulation protects the kidney against IR-induced injury by inhibiting endoplasmic reticulum stress-mediated autophagy. AJTR
Authors: Lin Wang; Nanhu Quan; Wanqing Sun; Xu Chen; Courtney Cates; Thomas Rousselle; Xinchun Zhou; Xuezhong Zhao; Ji Li Journal: Cardiovasc Res Date: 2018-05-01 Impact factor: 10.787