Renal ischemia-reperfusion is a major cause of acute kidney injury, a disease currently without effective treatments. Irisin was initially identified as an important factor produced by muscles to mediate the health benefits of exercise, and recent work has further suggested its protective effect against lung and liver injury. However, the role of Irisin in kidney diseases, including renal ischemia-reperfusion injury (IRI), remains unknown. In the present study, we found that the Irisin precursor, fibronectin type III domain-containing protein 5 (Fndc5), was induced in renal tubules in a mouse model of renal IRI and in cultured mouse renal proximal tubular cells subjected ATP depletion injury. Functionally, silencing Fndc5 in cultured proximal tubular cells increased the sensitivity to ATP depletion-induced apoptosis, whereas both Fndc5 overexpression and supplementation of recombinant Irisin alleviated ATP depletion-induced apoptosis. In vivo, administration of recombinant Irisin dramatically attenuated kidney dysfunction, tissue damage, tubular cell apoptosis, and inflammation during renal IRI in mice. Mechanistically, Irisin suppressed the activation of p53 in renal IRI, a critical factor in tubular cell death. Together, these results indicate that Irisin is induced in renal IRI as a protective mechanism for renal tubular cells, suggesting the therapeutic potential of recombinant Irisin in renal IRI and related kidney diseases.

中文翻译：

---

鸢尾素在肾缺血-再灌注中被诱导，以通过抑制p53来防止肾小管细胞损伤。

肾缺血-再灌注是急性肾损伤的主要原因，急性肾损伤是目前没有有效治疗的疾病。鸢尾素最初被认为是由肌肉产生的重要物质，可调节锻炼对健康的益处，最近的工作进一步表明其对肺和肝损伤的保护作用。然而，Irisin在包括肾脏缺血再灌注损伤（IRI）在内的肾脏疾病中的作用仍然未知。在本研究中，我们发现在肾IRI小鼠模型的肾小管中以及在遭受ATP耗竭损伤的培养的小鼠肾近端肾小管细胞中，诱导了鸢尾素前体，即含有纤连蛋白III型域的蛋白5（Fndc5）。功能上，在培养的近端肾小管细胞中沉默Fndc5可增加对ATP耗竭诱导的细胞凋亡的敏感性，而Fndc5的过表达和重组Irisin的补充均减轻了ATP耗竭诱导的细胞凋亡。在体内，重组Irisin的给药可显着减轻小鼠肾脏IRI期间的肾功能不全，组织损伤，肾小管细胞凋亡和炎症。从机理上讲，Irisin抑制了肾脏IRI中p53的激活，这是肾小管细胞死亡的关键因素。总之，这些结果表明在肾IRI中诱导了鸢尾素作为肾小管细胞的保护机制，表明重组鸢尾素在肾IRI和相关肾脏疾病中的治疗潜力。和小鼠肾脏IRI期间的炎症。从机理上讲，Irisin抑制了肾IRI（肾小管细胞死亡的关键因素）中p53的激活。总之，这些结果表明，在肾脏IRI中诱导鸢尾素是肾小管细胞的保护机制，表明重组鸢尾素在肾脏IRI和相关肾脏疾病中的治疗潜力。和小鼠肾脏IRI期间的炎症。从机理上讲，Irisin抑制了肾脏IRI中p53的激活，这是肾小管细胞死亡的关键因素。总之，这些结果表明在肾IRI中诱导了鸢尾素作为肾小管细胞的保护机制，表明重组鸢尾素在肾IRI和相关肾脏疾病中的治疗潜力。