Spatial composition and turnover of the main molecules in the adult glomerular basement membrane

The glomerular basement membrane (GBM) is an important tissue structure in kidney function. It is the membrane through which filtrate and solutes must pass to reach the nephron tubules. This review focuses on the spatial location of the main extracellular matrix components of the GBM. It also attempts to explain this organization in terms of their synthesis, transport, and loss. The picture that emerges is that the collagen IV and laminin content of GBM are in a very slow dynamic disequilibrium, leading to GBM thickening with age, and in contrast, some heparan sulfate proteoglycans are in a dynamic equilibrium with a very rapid turnover (i.e. half-life measured in ~hours) and flow direction against the flow of filtrate. The highly rapid heparan sulfate turnover may serve several roles, including an unclogging mechanism for the GBM, compressive stiffness of the GBM fiber network, and/or enabling podocycte-endothelial crosstalk against the flow of filtrate.