Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Int J Mol Sci. 2020 Feb 25;21(5):1559. doi: 10.3390/ijms21051559.
Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney. As a membrane-bound organelle, lysosomes are responsible for the degradation of molecules via hydrolytic enzymes. In addition to its degradative properties, recent studies have revealed that lysosomes may serve as a platform mediating cellular signaling in different types of cells. In the last decade, increasing evidence has revealed that the normal function of the lysosome is important for the maintenance of podocyte homeostasis. Podocytes have no ability to proliferate under most pathological conditions; therefore, lysosome-dependent autophagic flux is critical for podocyte survival. In addition, new insights into the pathogenic role of lysosome and associated signaling in podocyte injury and chronic kidney disease have recently emerged. Targeting lysosomal functions or signaling pathways are considered potential therapeutic strategies for some chronic glomerular diseases. This review briefly summarizes current evidence demonstrating the regulation of lysosomal function and signaling mechanisms as well as the canonical and noncanonical roles of podocyte lysosome dysfunction in the development of chronic glomerular diseases and associated therapeutic strategies.
足细胞是覆盖在肾脏肾小球毛细血管外表面的内脏上皮细胞。血液通过足细胞的裂孔隔膜滤过形成尿液。足细胞的功能和结构完整性对于肾脏的正常功能至关重要。溶酶体作为一种膜结合细胞器，通过水解酶负责分子的降解。除了其降解特性外，最近的研究表明，溶酶体可能作为一个平台，在不同类型的细胞中介导细胞信号转导。在过去的十年中，越来越多的证据表明溶酶体的正常功能对于维持足细胞内稳态很重要。在大多数病理条件下，足细胞没有增殖的能力；因此，溶酶体依赖性自噬流对于足细胞的存活至关重要。此外，最近人们对溶酶体及其相关信号在足细胞损伤和慢性肾脏病中的致病作用有了新的认识。靶向溶酶体功能或信号通路被认为是一些慢性肾小球疾病的潜在治疗策略。本文简要综述了目前的证据，证明了溶酶体功能和信号机制的调节，以及足细胞溶酶体功能障碍在慢性肾小球疾病发展中的典型和非典型作用，以及相关的治疗策略。
