Abstract

Diabetic nephropathy (DN) is a major microvascular complication of diabetes, and the loss of glomerular podocytes through apoptosis is a critical event in its progression. This review article systematically analyzes the current state of knowledge regarding the molecular mechanisms that drive podocyte apoptosis in the context of DN. The primary objective is to delineate the key intracellular signaling pathways activated by pathogenic factors such as chronic hyperglycemia, advanced glycation end-products (AGEs), oxidative stress, and endoplasmic reticulum (ER) stress. The analysis focuses on several pivotal pathways, including the Wnt/β-catenin pathway, the mTOR-dependent signaling pathway (mTORC1 and mTORC2), the Rho/ROCK signaling cascade, and various calcium-dependent pathways, particularly those involving TRPC family channels. Key findings indicate that the convergence of these stress factors triggers the activation of pro-apoptotic signals, ultimately leading to podocyte depletion and the characteristic pathology of DN. The significance of this work lies in providing a comprehensive framework for understanding podocyte survival and death, highlighting potential molecular targets for novel therapeutic strategies aimed at preserving podocyte integrity and slowing the progression of diabetic kidney disease.