Abstract：
OBJECTIVE: A myokine secreted by skeletal muscles during exercise called irisin mitigates ischemia-reperfusion (I/R) injury in epithelial cells of various organs by limiting damage to mitochondria. We test whether irisin may preserve the mitochondrial integrity and function in renal tubular epithelial cells and protect against ischemia-reperfusion-induced acute kidney injury (AKI).
METHODS: We correlated serum irisin levels with serum creatinine and BUN levels from both AKI patients and healthy individuals. In mice with irisin administration, various renal injury markers such as serum creatinine, BUN, kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL), and renal histopathology were assessed after I/R. To identify the potential mechanisms of the protective of irisin\'s protective effect, we perfused proximal tubules under confocal microscopy and analyzed kidney tissues by qPCR, western blot, and immunohistochemistry.
RESULTS: Serum irisin correlated inversely with serum creatinine and BUN levels were significantly lower in AKI patients than in healthy subjects. Administering irisin to mice after I/R decreased biomarker levels for AKI including serum creatinine, BUN, Kim-1, NAGL and lessened histological changes. In kidney tissues of mice, irisin upregulated the mitochondrial autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3), the mitochondrial autophagy pathway-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkinson\'s disease 2 parkin (PARK2) and downregulated the reactive substrate protein sequestosome 1 (P62) and mitochondrial membrane proteins translocase of outer mitochondrial membrane 20 (TOM20) and translocase of inner mitochondrial membrane 23 (TIM23).
CONCLUSIONS: Irisin protects against renal I/R injury, which may involve the preservation of mitochondrial integrity and function.
METHODS: We correlated serum irisin levels with serum creatinine and BUN levels from both AKI patients and healthy individuals. In mice with irisin administration, various renal injury markers such as serum creatinine, BUN, kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL), and renal histopathology were assessed after I/R. To identify the potential mechanisms of the protective of irisin\'s protective effect, we perfused proximal tubules under confocal microscopy and analyzed kidney tissues by qPCR, western blot, and immunohistochemistry.
RESULTS: Serum irisin correlated inversely with serum creatinine and BUN levels were significantly lower in AKI patients than in healthy subjects. Administering irisin to mice after I/R decreased biomarker levels for AKI including serum creatinine, BUN, Kim-1, NAGL and lessened histological changes. In kidney tissues of mice, irisin upregulated the mitochondrial autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3), the mitochondrial autophagy pathway-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkinson\'s disease 2 parkin (PARK2) and downregulated the reactive substrate protein sequestosome 1 (P62) and mitochondrial membrane proteins translocase of outer mitochondrial membrane 20 (TOM20) and translocase of inner mitochondrial membrane 23 (TIM23).
CONCLUSIONS: Irisin protects against renal I/R injury, which may involve the preservation of mitochondrial integrity and function.
摘要：
目的：骨骼肌在运动过程中分泌的一种名为irisin的肌肉因子通过限制线粒体的损伤来减轻各种器官上皮细胞的缺血再灌注（I/R）损伤。我们测试irisin是否可以保留肾小管上皮细胞的线粒体完整性和功能，并防止缺血再灌注诱导的急性肾损伤（AKI）。
方法：我们将AKI患者和健康个体的血清irisin水平与血清肌酐和BUN水平相关联。在服用irisin的小鼠中，各种肾损伤标志物，如血清肌酐，BUN,肾损伤分子-1（Kim-1），和中性粒细胞明胶酶相关脂质运载蛋白（NGAL），I/R后评估肾组织病理学为了确定irisin的保护作用的潜在机制，我们在共聚焦显微镜下灌注近端小管，并通过qPCR分析肾脏组织，westernblot,和免疫组织化学。
结果：AKI患者的血清irisin与血清肌酐呈负相关，BUN水平明显低于健康受试者。I/R后给小鼠服用irisin降低了AKI的生物标志物水平，包括血清肌酐，BUN,Kim-1、NAGL和减轻组织学改变。在小鼠的肾脏组织中，irisin上调线粒体自噬标记蛋白微管相关蛋白1轻链3(LC3),线粒体自噬途径相关蛋白PTEN诱导的推定激酶1（PINK1）和帕金森病2parkin（PARK2），并下调反应性底物蛋白隔离体1（P62）和线粒体外膜20的线粒体膜蛋白转位酶（TOM20）和线粒体内膜23的转位酶（TIM23）。
结论：Irisin保护肾脏I/R损伤，这可能涉及线粒体完整性和功能的保护。
方法：我们将AKI患者和健康个体的血清irisin水平与血清肌酐和BUN水平相关联。在服用irisin的小鼠中，各种肾损伤标志物，如血清肌酐，BUN,肾损伤分子-1（Kim-1），和中性粒细胞明胶酶相关脂质运载蛋白（NGAL），I/R后评估肾组织病理学为了确定irisin的保护作用的潜在机制，我们在共聚焦显微镜下灌注近端小管，并通过qPCR分析肾脏组织，westernblot,和免疫组织化学。
结果：AKI患者的血清irisin与血清肌酐呈负相关，BUN水平明显低于健康受试者。I/R后给小鼠服用irisin降低了AKI的生物标志物水平，包括血清肌酐，BUN,Kim-1、NAGL和减轻组织学改变。在小鼠的肾脏组织中，irisin上调线粒体自噬标记蛋白微管相关蛋白1轻链3(LC3),线粒体自噬途径相关蛋白PTEN诱导的推定激酶1（PINK1）和帕金森病2parkin（PARK2），并下调反应性底物蛋白隔离体1（P62）和线粒体外膜20的线粒体膜蛋白转位酶（TOM20）和线粒体内膜23的转位酶（TIM23）。
结论：Irisin保护肾脏I/R损伤，这可能涉及线粒体完整性和功能的保护。
