Inherited diseases of the glomerular basement membrane.
The glomerular basement membrane (GBM) is a specialized form of basement membrane that has a major role in the maintenance of the glomerular filtration barrier. Like all basement membranes, it contains four main components: type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. Different isoforms of these large molecules are produced. These isoforms have a tissue-specific distribution; in the mature GBM, the major type IV collagen molecule is the alpha 3 alpha 4 alpha 5(IV) isoform, associated with laminin-521 (alpha 5 beta2 gamma 1), nidogen and agrin heparan sulfate proteoglycans. The importance of the GBM has been demonstrated by identification of hereditary glomerular diseases linked to structural anomalies of its components; for example, type IV collagen in Alport syndrome and familial benign hematuria, and laminin in Pierson syndrome. Type III collagen, an interstitial collagen, accumulates within the GBM of patients with the nail-patella syndrome, and abnormal deposition of fibronectin, another extracellular matrix protein, is characteristic of so-called fibronectin nephropathy. Development of animal models of these diseases has facilitated precise analysis of pathogenic mechanisms, but no specific treatments are available. Therapeutic trials in Alport syndrome nephropathy are underway, following promising preliminary results obtained in rodent and canine models of the disorder.
Gubler
Marie Claire
MC
Institut National de la Santé et de la Recherche Médicale, INSERM U574, Hôpital Necker-Enfants Malades, Paris F75015, France. gubler@necker.fr
D000818:Animals; D024061:Collagen Type III / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics; D005353:Fibronectins / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000473:pathology; D006417:Hematuria / Q000235:genetics / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D007797:Laminin / Q000235:genetics; D009154:Mutation; D009261:Nail-Patella Syndrome / Q000378:metabolism; D009394:Nephritis, Hereditary / Q000235:genetics / Q000473:pathology; D010641:Phenotype
D024061:Collagen Type III; D024141:Collagen Type IV; D005353:Fibronectins; D007797:Laminin; C058783:laminin beta2