title: Involvement of MCP-1 in tubulointerstitial fibrosis through massive proteinuria in anti-GBM nephritis induced in WKY rats.
abstract: We investigated participation of monocyte chemoattractant protein-1 (MCP-1) in tubulointerstitial fibrosis and correlation between MCP-1 and proteinuria in Wistar-Kyoto (WKY) rats with glomerulonephritis induced by anti-glomerular basement membrane (anti-GBM) antibody. WKY rats showed marked proteinuria and severe glomerular crescent formation at 7 days post antibody injection. At 28 days, tubulointerstitial fibrotic lesions were observed, followed by sustained heavy proteinuria and severe tubulointerstitial fibrosis at 56 days. Histological examination revealed that the overlapped immunoreactivities of MCP-1, rat albumin, and p65NF-kappaB were detected in the same tubular segments of nephritic kidney, and a significant positive correlation was observed between proteinuria and MCP-1 expression in the tubulointerstitial fibrosis. ED-1- and CD8-positive cells were also abundant, and there was a good correlation between monocyte/macrophage recruitment and MCP-1 expression in the tubulointerstitial area. These results suggest that MCP-1 participates in the progression of tubulointerstitial fibrosis, through massive albuminuria, which is accompanied by marked monocyte/macrophage recruitment.
authors.affiliation: Biomedical Research Laboratories, Daiichi Asubio Pharma Co., Ltd., Osaka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kojima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sade
authors.forename: Mayumi
authors.initials: M
authors.lastname: Furuya
authors.forename: Norio
authors.initials: N
authors.lastname: Inomata
authors.forename: Mikio
authors.initials: M
authors.lastname: Ito
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000139:chemically induced / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology* / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D007668:Kidney / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000276:immunology*; D011507:Proteinuria / Q000139:chemically induced / Q000276:immunology* / Q000652:urine; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016212:Transforming Growth Factor beta; D003404:Creatinine