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. Glomer ular deposition of clusterin has been observed in human and experimental me mbranous nephropathy in association with C5b-9 and immune deposits. However , it is controversial as to whether clusterin observed in glomeruli is synt hesized by the resident glomerular cells or is derived from the circulation . We examined whether clusterin is expressed by resident glomerular cells e xposed to complement-mediated injury. Methods. In vitro, cultured mesangial cells were exposed to antithymocyte s erum immunoglobulin G and 5% normal rat serum as a complement source. In vi vo, we induced anti-TTy1 nephritis in rats and examined the kidneys on days 8 and 29. Results. We observed increased expression of clusterin in cultured rat glom erular mesangial cells stimulated by sublytic complement attack. We also de monstrated 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 associa tion with C5b-9 deposition and on day 29. Conclusion. Clusterin was induced in glomerular mesangial cells during the course of immune-mediated injuries. This upregulation of clusterin may play a critical role in protecting mesangial cells from complement attack.