Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury.
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.
Yamada
K
K
Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Hori
Y
Y
Hanafusa
N
N
Okuda
T
T
Nagano
N
N
Choi-Miura
N H
NH
Couser
W G
WG
Miyata
T
T
Kurokawa
K
K
Fujita
T
T
Nangaku
M
M
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
D000961:Antilymphocyte Serum; D051152:Clusterin; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D007074:Immunoglobulin G; D018832:Molecular Chaperones; D012333:RNA, Messenger