Abstract
Proteinuria is observed in various kidney diseases and is frequently associated with a compromised glomerular filtration barrier. Podocytes, as a crucial component of this barrier, play an essential role in preserving the kidney's normal filtration function. Podocytes are terminally differentiated cells that typically do not proliferate. However, certain harmful stimuli can trigger podocytes to re-enter the cell cycle. Due to its unique cytoskeletal structure, podocytes are unable to maintain the structure of the foot process and complete cell division at the same time, eventually form binucleated or multinucleated podocytes. Studies have found that podocytes re-entering the cell cycle are more susceptible to injury, and are prone to detachment from the basement membrane or apoptosis, which are accompanied by the widening of foot processes. This eventually leads to podocyte mitotic catastrophe and the development of proteinuria. Podocyte cell cycle disorders have previously been found mainly in focal segmental glomerulosclerosis and IgA nephropathy. In recent years, this phenomenon has been frequently identified in diabetic kidney disease and lupus nephritis. An expanding body of research has begun to investigate the mechanisms underlying podocyte cell cycle disorders, including cell cycle re-entry, cell cycle arrest, and mitotic catastrophe. This review consolidates the existing literature on podocyte cell cycle disorders in renal diseases and summarizes the molecules that trigger podocyte re-entry into the cell cycle, thereby providing new drug targets for mitigating podocyte damage. This is essential for alleviating podocyte injury, reducing proteinuria, and delaying the progression of kidney diseases.