Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, U.S.A.
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, U.S.A.
Clin Sci (Lond). 2024 Aug 7;138(15):963-973. doi: 10.1042/CS20231331.
Renal tubules have potential to regenerate and repair after mild-to-moderate injury. Proliferation of tubular epithelial cells represents the initial step of this reparative process. Although for many years, it was believed that proliferating cells originated from a pre-existing intra-tubular stem cell population, there is now consensus that surviving tubular epithelial cells acquire progenitor properties to regenerate the damaged kidney. Scattered tubular-like cells (STCs) are dedifferentiated adult renal tubular epithelial cells that arise upon injury and contribute to renal self-healing and recovery by replacing lost neighboring tubular epithelial cells. These cells are characterized by the co-expression of the stem cell surface markers CD133 and CD24, as well as mesenchymal and kidney injury markers. Previous studies have shown that exogenous delivery of STCs ameliorates renal injury and dysfunction in murine models of acute kidney injury, underscoring the regenerative potential of this endogenous repair system. Although STCs contain fewer mitochondria than their surrounding terminally differentiated tubular epithelial cells, these organelles modulate several important cellular functions, and their integrity and function are critical to preserve the reparative capacity of STCs. Recent data suggest that the microenviroment induced by cardiovascular risk factors, such as obesity, hypertension, and renal ischemia may compromise STC mitochondrial integrity and function, limiting the capacity of these cells to repair injured renal tubules. This review summarizes current knowledge of the contribution of STCs to kidney repair and discusses recent insight into the key role of mitochondria in modulating STC function and their vulnerability in the setting of cardiovascular disease.
肾小管在轻度到中度损伤后具有再生和修复的潜力。管状上皮细胞的增殖代表了这个修复过程的初始步骤。尽管多年来，人们一直认为增殖细胞来源于预先存在的管腔内干细胞群体，但现在已经达成共识，即存活的管状上皮细胞获得祖细胞特性，以再生受损的肾脏。散在的管状样细胞（STCs）是分化的成年肾小管上皮细胞，在损伤时出现，并通过替代丢失的相邻肾小管上皮细胞来促进肾脏的自我修复和恢复。这些细胞的特征是干细胞表面标记物 CD133 和 CD24 的共表达，以及间充质和肾脏损伤标记物。先前的研究表明，外源性 STCs 的递送可改善急性肾损伤小鼠模型中的肾损伤和功能障碍，强调了这种内源性修复系统的再生潜力。尽管 STCs 比其周围的终末分化管状上皮细胞含有更少的线粒体，但这些细胞器调节着几个重要的细胞功能，其完整性和功能对于维持 STCs 的修复能力至关重要。最近的数据表明，心血管危险因素（如肥胖、高血压和肾缺血）诱导的微环境可能会损害 STC 线粒体的完整性和功能，限制这些细胞修复受损肾小管的能力。本综述总结了 STCs 对肾脏修复的贡献的现有知识，并讨论了最近关于线粒体在调节 STC 功能及其在心血管疾病中的脆弱性方面的关键作用的新见解。
