Tubular up-regulation of clusterin mRNA in murine lupus-like nephritis.
Clusterin, a widely distributed glycoprotein, is detected in most tissues and in numerous physiological fluids. In the kidney, this protein is constitutively expressed in tubular epithelial cells, and its expression is enhanced following tubular injuries. In addition, clusterin has been detected in glomerular immune deposits of glomerulonephritis. The present study was designed to define the sites of clusterin mRNA accumulation in murine lupus-like nephritis in comparison with murine tubulopathies. In lupus-like nephritis, a significant increase of clusterin mRNA abundance was demonstrated. This up-regulation was localized exclusively in tubular epithelial cells exhibiting tubulointerstitial alterations, whereas no clusterin mRNA was detectable in diseased glomeruli, excluding an active synthesis of clusterin by glomerular cells. A similar tubular increase of clusterin mRNA abundance was observed in myeloma-like cast nephropathy induced by IgG3 monoclonal cryoglobulins and even in the absence of any detectable histological alterations in a model of septic shock induced by the injection of bacterial lipopolysaccharides. Our results suggest that tubular epithelial cells are the only sites of clusterin mRNA accumulation during the course of lupus-like nephritis and that the tubular up-regulation of clusterin gene expression may reflect the cellular response to various types of tubular injuries.
Moll
S
S
Department of Internal Medicine, University of Geneva Medical School, Switzerland.
Menoud
P A
PA
French
L
L
Sappino
A P
AP
Pastore
Y
Y
Schifferli
J A
JA
Izui
S
S
D000818:Animals; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G / Q000009:adverse effects; D017403:In Situ Hybridization; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects; D008177:Lupus Vulgaris / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018832:Molecular Chaperones; D009393:Nephritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
C495243:Clu protein, mouse; D051152:Clusterin; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger