Renal Nephropathy: Distinct Role of Protein Kinase C in Podocyte Function

A crippling consequence of diabetes mellitus is diabetic nephropathy (DN). It is deterioration of kidney function and its final stage is called kidney failure or end-stage renal disease. The malfunction of podocytes, which are specialized epithelial cells lining the kidney's glomerular filtration barrier, is central to the pathogenesis of DN. The critical function of Protein Kinase C (PKC) isoenzymes in podocytes and its complex participation in DN have been clarified by recent research. This review provides a thorough synopsis of the subject. The slit diaphragm (SD), which anchors the glomerular filtration barrier, is essential to the barrier's structural integrity and operation because of its precise molecular composition. The PKC isoenzymes have become important regulators of podocyte function, including PKC-α, PKC-β, new PKCs (δ and ε), and atypical PKCs (γ and ζ). The PKC-α and PKC-β have been linked to the development of DN through their roles in microvascular contraction, basement membrane thickening, and the production of extracellular matrix proteins (ECMP). On the other hand, new PKCs have complex actions, and PKC-ε may have a protective function. In podocytes, atypical PKCs are crucial for establishing cell polarity and protein transport. Furthermore, in high-glucose environments, PKC isoenzymes interact with β-catenin to affect adherens junctions at the SD and cause podocyte damage. As a potential treatment approach to slow the course of DN, targeting particular PKC isoforms has shown promise. The complex interactions between PKC isoenzymes and podocytes in the setting of DN are outlined in this review, emphasizing their functions in protein trafficking, ECMP production, and glomerular filtration. A thorough understanding of these molecular interactions can help to understand the pathophysiology of DN and pave the way for future treatment approaches. To develop more focused and efficient therapies for DN, more investigation is necessary to determine the particular roles played by each PKC isoform.