Glomerular basement membrane and related glomerular disease

Abstract

The glomerular basement membrane (GBM) is lined by fenestrated endothelium from the capillary-lumen side and by interdigitating foot processes of the podocytes from the urinary-space side. These three layers of the glomerular capillary wall constitute the functional unit of the glomerular filtration barrier. The GBM is assembled through an interweaving of type IV collagen with laminins, nidogen, and sulfated proteoglycans. Mutations in genes encoding LAMB2, COL4A3, COL4A4, and COL4A5 cause glomerular disease in humans as well as in mice. In addition, laminin α5 mutation in podocytes leads to proteinuria and renal failure in mice. Moreover, more neoepitopes in Goodpasture’s disease and for the first time alloepitopes in Alport post-transplantation nephritis have been located in the collagen α5(IV) NC1 domain. These discoveries underscore the importance of the GBM in establishing and maintaining the integrity of the glomerular filtration barrier.

The glomerular basement membrane as a barrier to albumin

“…Laminin trimers assemble and become glycosylated in the endoplasmic reticulum and are processed further in the Golgi apparatus. 30 After secretion into the extracellular space, laminin trimers self-polymerize to form a laminin network by interactions among LN domains. 20 This polymerization step is a reversible and calcium-dependent process that requires a critical concentration of laminin trimers to form an initiating complex.…”

A NovelCOL4A5Mutation Identified in a Chinese Han Family Using Exome Sequencing

“…Once the α 5 chain is missing, the formation of the normal α 3 α 4 α 5 (IV) protomer is disrupted in BM of glomerulus, ear, eye, and lung, which could lead to structural and functional defects [23]. This is supported by the immunohistochemical finding of frequent loss of α 3, α 4, and α 5 signals in the GBM of XLAS patients [24, 25]. The cause of clinical heterogeneity of XLAS, such as difference in age of disease onset, disease severity, and disease progression, may be multifactorial, including random X chromosome inactivation, ethnic background, and environment factors.…”

The Role of Extracellular Matrix Proteins in the Urinary Tract: A Literature Review

“…Once trimerization completed they are secreted into the extracel-lular space and they polymerize to form a supramolecular network. Laminin polymerization initiates basement membrane formation and sends signal to adjacent cells [7].…”

“…In normal physiologic conditions, ECM of glomerular mesangium consists of fibronectin, collagen type IV, collagen type V, laminin, chondroitin sulfate, heparan sulfate and nidogen [7,17]. Mesangial ECM allows larger molecules to pass to the mesangium in contrast to glomerular basal membrane.…”