title: Complement regulatory proteins in glomerular diseases.
abstract: Complement activation plays a critical role in the pathogenesis of many forms of glomerulonephritis. Complement activation leads to tissue injury through various mechanisms including the generation of chemotactic factors and activation of the resident glomerular cells following C5b-9 insertion. Recent advances have disclosed the mechanisms of regulation of complement activation by discovery of a number of complement regulatory proteins. Decay accelerating factor (DAF), membrane cofactor protein (MCP), and complement receptor type 1 (CR1) act by inactivating C3/C5 convertase. They belong to the gene superfamily known as the regulators of complement activation (RCA), and share a common structural motif called a short consensus repeat (SCR). In contrast, CD59 works by inhibiting formation of C5b-9. The glomerulus is particularly well endowed with these membrane-bound complement regulatory proteins. DAF, MCP, and CD59 are ubiquitously expressed by all three resident glomerular cells, while CR1 is localized exclusively in podocytes. Expression of complement regulatory proteins can be changed by many factors including complement attack itself, and their expression levels are affected in various glomerular disorders. Studies utilizing cultured glomerular cells and animal models of glomerular diseases suggest important protective roles of complement regulatory proteins against immune-mediated renal injury. Recent progress in molecular biological techniques has made new therapeutic strategy feasible. Systemic administration of soluble recombinant complement regulatory proteins and local overexpression of complement regulatory proteins are promising therapeutic approaches.
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan. mnangaku-tky@umin.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018958:CD55 Antigens / Q000502:physiology; D018957:CD59 Antigens / Q000502:physiology; D003167:Complement Activation; D005921:Glomerulonephritis / Q000276:immunology* / Q000628:therapy; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000502:physiology; D011951:Receptors, Complement / Q000502:physiology; D017463:Receptors, Complement 3b / Q000502:physiology
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b