Wang Yanjun, Ding Yanling, Dong Haiyun, Wuren Tana, Luo Pengli
Department of Geriatrics, Affiliated Hospital of Qinghai University, Xining, Qinghai, 810001, China; Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai, 810001, China; High-Altitude Medicine Key Laboratory of the Ministry of Education, Xining, Qinghai, 810001, China; Qinghai Provincial Key Laboratory for Application of High-Altitude Medicine (Qinghai-Utah Joint Key Laboratory for Plateau Medicine), Xining, Qinghai, 810001, China.
Department of Nephrology, Affiliated Hospital of Qinghai University, Xining, Qinghai, 810001, China.
Exp Cell Res. 2025 Jul 15;450(2):114583. doi: 10.1016/j.yexcr.2025.114583. Epub 2025 May 3.
This study aims to investigate the mechanisms of MSC therapy for acute kidney injury, focusing on the regulation of mitochondrial function and pyroptosis in renal tubular epithelial cells (RTECs).
An in vivo ischemia/reperfusion (I/R) model was used to assess the effects of MSC treatment on mitochondrial membrane potential, mitochondrial function, cell pyroptosis, and PGC-1α expression in RTECs.
MSCs significantly improved mitochondrial function in RTECs by upregulating PGC-1α expression, regulating mitochondrial fusion and fission proteins, reducing mitochondrial ROS production, and suppressing NLRP3 inflammasome activation. Furthermore, MSC treatment reduced the levels of pyroptotic markers, such as IL-18, and exhibited a marked anti-fibrotic effect in the long-term. These findings suggest that MSCs not only repair acute kidney injury but also offer long-term protection against fibrosis.
MSCs improve the repair of acute kidney injury by modulating mitochondrial function and inhibiting pyroptosis, providing new theoretical support for MSC-based therapies in AKI treatment.
本研究旨在探讨间充质干细胞（MSC）治疗急性肾损伤的机制，重点关注其对肾小管上皮细胞（RTECs）线粒体功能和细胞焦亡的调控。
采用体内缺血/再灌注（I/R）模型评估MSC治疗对RTECs线粒体膜电位、线粒体功能、细胞焦亡及PGC-1α表达的影响。
MSC通过上调PGC-1α表达、调节线粒体融合与裂变蛋白、减少线粒体活性氧生成及抑制NLRP3炎性小体激活，显著改善了RTECs的线粒体功能。此外，MSC治疗降低了细胞焦亡标志物如IL-18的水平，并在长期显示出明显的抗纤维化作用。这些发现表明，MSC不仅能修复急性肾损伤，还能提供长期的抗纤维化保护。
MSC通过调节线粒体功能和抑制细胞焦亡改善急性肾损伤的修复，为基于MSC的急性肾损伤治疗提供了新的理论支持。
