title: Collagen IV diseases: A focus on the glomerular basement membrane in Alport syndrome.
abstract: Alport syndrome is the result of mutations in any of three type IV collagen genes, COL4A3, COL4A4, or COL4A5. Because the three collagen chains form heterotrimers, there is an absence of all three proteins in the basement membranes where they are expressed. In the glomerulus, the mature glomerular basement membrane type IV collagen network, normally comprised of two separate networks, α3(IV)/α4(IV)/α5(IV) and α1(IV)/α2(IV), is comprised entirely of collagen α1(IV)/α2. This review addresses the current state of our knowledge regarding the consequence of this change in basement membrane composition, including both the direct, via collagen receptor binding, and indirect, regarding influences on glomerular biomechanics. The state of our current understanding regarding mechanisms of glomerular disease initiation and progression will be examined, as will the current state of the art regarding emergent therapeutic approaches to slow or arrest glomerular disease in Alport patients.
authors: Boys Town National Research Hospital, Omaha, NE, USA. Electronic address: dominic.cosgrove@boystown.org.
authors: Dominic
authors: D
authors: Cosgrove
authors: Sanofi-Genzyme R&D Center, Framingham, MA, USA.
authors: Shiguang
authors: S
authors: Liu
mesh_terms: D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D024141:Collagen Type IV / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D055503:Protein Multimerization; D038981:Receptors, Collagen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001324:Autoantigens; C466620:COL4A4 protein, human; C478159:COL4A5 protein, human; D024141:Collagen Type IV; C579157:ITGA8 protein, human; D039001:Integrin alpha Chains; D038981:Receptors, Collagen; C057112:type IV collagen alpha3 chain