Irisin preserves mitochondrial integrity and function in tubular epithelial cells after ischemia–reperfusion-induced acute kidney injury

IF 5.6 2区医学 Q1 PHYSIOLOGY

Acta Physiologica Pub Date : 2024-07-29 DOI:10.1111/apha.14211

Yu Cui, Lu Yu, Wenqi Cong, Shan Jiang, Xingyu Qiu, Chunchun Wei, Gui Zheng, Jianhua Mao, Ruisheng Liu, Andreas Patzak, Pontus B. Persson, Jianghua Chen, Liang Zhao, En Yin Lai

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引用次数: 0

Abstract

Aims

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).

Conclusion

Irisin protects against renal I/R injury, which may involve the preservation of mitochondrial integrity and function.

Abstract Image

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缺血再灌注诱发急性肾损伤后，鸢尾素能保护肾小管上皮细胞线粒体的完整性和功能。

目的：骨骼肌在运动过程中分泌的一种肌动素称为鸢尾素，它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损伤。我们测试了鸢尾素是否能保护肾小管上皮细胞线粒体的完整性和功能，并防止缺血再灌注引起的急性肾损伤（AKI）：我们将 AKI 患者和健康人的血清鸢尾素水平与血清肌酐和尿素氮水平相关联。在给小鼠注射鸢尾素后，评估了I/R后的各种肾损伤指标，如血清肌酐、BUN、肾损伤分子-1（Kim-1）、中性粒细胞明胶酶相关脂褐质（NGAL）和肾组织病理学。为了确定鸢尾素保护作用的潜在机制，我们在共聚焦显微镜下灌注了近端肾小管，并通过qPCR、Western印迹和免疫组化分析了肾组织：结果：AKI 患者血清鸢尾素与血清肌酐成反比，BUN 水平明显低于健康人。给I/R后的小鼠注射鸢尾素能降低AKI的生物标志物水平，包括血清肌酐、BUN、Kim-1和NAGL，并减轻组织学变化。在小鼠肾组织中，鸢尾素能上调线粒体自噬标记蛋白微管相关蛋白 1 轻链 3（LC3）、在小鼠肾脏组织中，鸢尾素上调线粒体自噬标记蛋白微管相关蛋白 1 轻链 3（LC3）、线粒体自噬通路相关蛋白 PTEN 诱导的假定激酶 1（PINK1）和帕金森病 2 帕金蛋白（PARK2），下调反应性底物蛋白序列组 1（P62）和线粒体膜蛋白线粒体外膜转运酶 20（TOM20）和线粒体内膜转运酶 23（TIM23）。结论鸢尾素能防止肾脏I/R损伤，这可能与线粒体完整性和功能的保护有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Physiologica 医学-生理学

CiteScore

11.80

自引率

15.90%

发文量

182

审稿时长

4-8 weeks

期刊介绍： Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.