Role of the Podocyte (and Glomerular Endothelium) in Building the GBM

摘要

This article summarizes the basic cellular and extracellular events in the development of the glomerulus and assembly of the glomerular basement membrane (GBM), paying special attention to laminin (LM) and type IV collagen. Cellular receptors for GBM proteins, including the integrins, dystroglycan, and discoidin domain receptor 1 also are discussed. Evidence is reviewed showing that the laminin isoform present in the earliest GBM, LM-111, and final isoform found in the mature GBM, LM-521, are each derived from both endothelial cells and podocytes. Although the early collagen α1α2α1(IV) similarly derives from endothelial cells and podocytes, collagen α3α4α5(IV) found in fully mature GBM is a product solely of podocytes. Genetic diseases affecting laminin and type IV collagen synthesis also are presented, with an emphasis on mutations to LAMB2 (Pierson syndrome) and COL4A3, COL4A4, and COL4A5 (Alport syndrome), and their experimental mouse models. Stress is placed on the assembly of a compositionally correct GBM for the acquisition and maintenance of glomerular barrier properties.