Department of Urology, The First Hospital of Jilin University, Changchun 130021, China.
Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
Metabolism. 2024 Jun;155:155913. doi: 10.1016/j.metabol.2024.155913. Epub 2024 Apr 11.
Renal fibrosis, specifically tubulointerstitial fibrosis, represents the predominant pathological consequence observed in the context of progressive chronic kidney conditions. The pathogenesis of renal fibrosis encompasses a multifaceted interplay of mechanisms, including but not limited to interstitial fibroblast proliferation, activation, augmented production of extracellular matrix (ECM) components, and impaired ECM degradation. Notably, mitochondria, the intracellular organelles responsible for orchestrating biological oxidation processes in mammalian cells, assume a pivotal role within this intricate milieu. Mitochondrial dysfunction, when manifest, can incite a cascade of events, including inflammatory responses, perturbed mitochondrial autophagy, and associated processes, ultimately culminating in the genesis of renal fibrosis. This comprehensive review endeavors to furnish an exegesis of mitochondrial pathophysiology and biogenesis, elucidating the precise mechanisms through which mitochondrial aberrations contribute to the onset and progression of renal fibrosis. We explored how mitochondrial dysfunction, mitochondrial cytopathy and mitochondrial autophagy mediate ECM deposition and renal fibrosis from a multicellular perspective of mesangial cells, endothelial cells, podocytes, macrophages and fibroblasts. Furthermore, it succinctly encapsulates the most recent advancements in the realm of mitochondrial-targeted therapeutic strategies aimed at mitigating renal fibrosis.
肾纤维化，特别是肾小管间质纤维化，是渐进性慢性肾病中观察到的主要病理后果。肾纤维化的发病机制包括多种机制的相互作用，包括但不限于间质成纤维细胞增殖、活化、细胞外基质 (ECM) 成分的产生增加以及 ECM 降解受损。值得注意的是，线粒体是负责在哺乳动物细胞中协调生物氧化过程的细胞内器官，在这个复杂的环境中起着关键作用。当线粒体功能障碍出现时，会引发一系列事件，包括炎症反应、线粒体自噬失调和相关过程，最终导致肾纤维化的发生。本综述旨在阐述线粒体病理生理学和生物发生的机制，阐明线粒体异常导致肾纤维化发生和进展的确切机制。我们从系膜细胞、内皮细胞、足细胞、巨噬细胞和成纤维细胞的多细胞角度探讨了线粒体功能障碍、线粒体细胞病变和线粒体自噬如何介导 ECM 沉积和肾纤维化。此外，它还简要总结了最近在针对肾纤维化的线粒体靶向治疗策略领域的进展。
