title: Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury.
abstract: BACKGROUND
  Clusterin is a soluble complement regulatory protein that binds to C5b-7 and inhibits generation of membrane attack complex, C5b-9. Glomerular deposition of clusterin has been observed in human and experimental membranous nephropathy in association with C5b-9 and immune deposits. However, it is controversial as to whether clusterin observed in glomeruli is synthesized by the resident glomerular cells or is derived from the circulation. We examined whether clusterin is expressed by resident glomerular cells exposed to complement-mediated injury.
  
  
  METHODS
  In vitro, cultured mesangial cells were exposed to antithymocyte serum immunoglobulin G and 5% normal rat serum as a complement source. In vivo, we induced anti-Thy1 nephritis in rats and examined the kidneys on days 8 and 29.
  
  
  RESULTS
  We observed increased expression of clusterin in cultured rat glomerular mesangial cells stimulated by sublytic complement attack. We also demonstrated that in comparison with control rats, both a marked increase in clusterin mRNA in the glomeruli and marked deposition of clusterin protein in the mesangial area occurred in the OX-7-treated rats on day 8 in association with C5b-9 deposition and on day 29.
  
  
  CONCLUSIONS
  Clusterin was induced in glomerular mesangial cells during the course of immune-mediated injuries. This up-regulation of clusterin may play a critical role in protecting mesangial cells from complement attack.
authors.affiliation: Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Hori
authors.forename: N
authors.initials: N
authors.lastname: Hanafusa
authors.forename: T
authors.initials: T
authors.lastname: Okuda
authors.forename: N
authors.initials: N
authors.lastname: Nagano
authors.forename: N H
authors.initials: NH
authors.lastname: Choi-Miura
authors.forename: W G
authors.initials: WG
authors.lastname: Couser
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000276:immunology; D051152:Clusterin; D015938:Complement Membrane Attack Complex / Q000378:metabolism / Q000502:physiology*; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009393:Nephritis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D000961:Antilymphocyte Serum; D051152:Clusterin; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D007074:Immunoglobulin G; D018832:Molecular Chaperones; D012333:RNA, Messenger