Central role of podocytes in mediating cellular cross talk in glomerular health and disease

Abstract

Podocytes are highly specialized epithelial cells that surround the capillaries of the glomeruli in the kidney. Together with the glomerular endothelial cells, these postmitotic cells are responsible for regulating filtrate from the circulating blood with their organized network of interdigitating foot processes that wrap around the glomerular basement membrane. Although podocyte injury and subsequent loss is the hallmark of many glomerular diseases, recent evidence suggests that the cell-cell communication between podocytes and other glomerular and nonglomerular cells is critical for the development and progression of kidney disease. In this review, we highlight these key cellular pathways of communication and how they might be a potential target for therapy in glomerular disease. We also postulate that podocytes might serve as a central hub for communication in the kidney under basal conditions and in response to cellular stress, which may have implications for the development and progression of glomerular diseases.

Keywords: cellular cross talk; glomerular diseases; kidney disease; podocytes.

Graphical abstract

Figure 1.

Visualization of a kidney glomerulus highlighting podocyte interactions with other kidney cell types. Podocytes have been shown to be the central mediators of several communication pathways with various kidney cell types, namely, 1) parietal epithelial cells, 2) glomerular endothelial cells, 3) proximal tubule cells, 4) juxtaglomerular cells, 5) mesangial cells, and 6) podocytes. Podocyte-specific ligand receptor interactions are shown in blue, green indicates podocyte-juxtaglomerular cells interactions, orange indicates secondary effectors, the red circular arrow indicates autocrine signaling, and double-sided arrows indicate structural/contact interaction. [The image was created with BioRender.com.]