Abstract：
Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.
摘要：
急性肾损伤（AKI）是肾功能的突然下降，可归因于活性氧（ROS）产生失调和线粒体功能受损。Irisin,骨骼肌对体力活动的反应分泌的一种I型膜蛋白，据报道，通过调节线粒体生物发生和氧化代谢来减轻肾脏损伤。在这项研究中,巨噬细胞膜涂层的金属有机框架（MCM@MOF）被开发作为封装irisin的纳米载体，以克服irisin的固有特性，包括短的循环时间，有限的肾脏靶向能力，和低的膜渗透性。由于巨噬细胞膜蛋白的保存,工程化的irisin介导的仿生纳米治疗剂具有延长的循环时间和增强的针对受损肾脏的靶向能力。irisin包裹的仿生纳米治疗剂通过保护线粒体功能和调节肾小管上皮细胞中的SOD2水平，有效减轻急性缺血再灌注损伤。本研究为推进irisin作为AKI的潜在治疗方法的发展提供了新的见解。
