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Titolo:
Up-regulation of glomerular extracellular matrix and transforming growth factor-beta expression in RF/J mice
Autore:
Kamata, T; Muso, E; Yashiro, M; Kawamura, T; Oyama, A; Matsushima, H; Takeuchi, E; Yoshida, H; Sasayama, S;
Indirizzi:
Kyotoanniv, Grad Sch Med, Dept Cardiovasc Med, Sakyo Ku, Kyoto 6068397, Jap Kyoto Univ Kyoto Japan 6068397 diovasc Med, Sakyo Ku, Kyoto 6068397, Jap Kyoto City Hosp, Kyoto, Japan Kyoto City Hosp Kyoto JapanKyoto City Hosp, Kyoto, Japan Shiga Med Ctr Adult Dis, Tokyo, Japan Shiga Med Ctr Adult Dis Tokyo Japan iga Med Ctr Adult Dis, Tokyo, Japan Kitano Hosp, Osaka, Japan Kitano Hosp Osaka JapanKitano Hosp, Osaka, Japan
Titolo Testata:
KIDNEY INTERNATIONAL
fascicolo: 3, volume: 55, anno: 1999,
pagine: 864 - 876
SICI:
0085-2538(199903)55:3<864:UOGEMA>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS; COMPLEMENTARY-DNA; IMMUNE-COMPLEXES; GENE-EXPRESSION; IGA DEPOSITION; IV COLLAGENASE; DDY MICE; TGF-BETA; SEQUENCE; NEPHRITIS;
Keywords:
glomerulosclerosis; collagen type I and IV; laminin; transforming growth factor-beta; extracellular matrix; protein turnover;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Muso, E Kyotooin,v, Grad Sch Med, Dept Cardiovasc Med, Sakyo Ku, 54 KawaraCho Shog Kyoto Univ 54 Kawara Cho Shogoin Kyoto Japan 6068397 ara Cho Shog
Citazione:
T. Kamata et al., "Up-regulation of glomerular extracellular matrix and transforming growth factor-beta expression in RF/J mice", KIDNEY INT, 55(3), 1999, pp. 864-876

Abstract

Background RF/J mice were first reported as a murine model of spontaneous glomerulosclerosis by Gude and Lupton in 1960, but the precise histologic characteristics and immunopathological background of this mouse have not been investigated further. Methods. Measurements of serum levels of immunoglobulins, anti-single strand DNA (anti-ss-DNA) antibody, complement (C-3), and circulating immune complex (IC) were performed. Analyses of glomerular histological and immunopathological lesions in association with the detection of mRNA expression of collagen IV, TGF-P, matrix protein turnover related enzymes, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) and platelet-derived growth factor (PDGF) were also performed in young (10-week-old) and elderly (60-week-old) RF/J mice with age-matched BALB/C mice as the controls. Results. High levels of serum IgA and IgG from as early as 20 weeks of agewere noted in the RF/J mice. Serum anti-ss-DNA antibody of aged RF/J mice increased up to 23% of that of aged MRL-lpr/lpr mice, and serum C-3 concentration significantly decreased with age, reaching lower levels than that ofBALB/c mice. IgA-IC levels were significantly high compared to BALB/C miceboth in the early and late stages of life, whereas IgG-IC levels were highonly in mice younger than 20 weeks. Semiquantitative and quantitative analyzes of renal histopathological findings revealed significantly marked and age-related mesangial matrix expansion in RF/J mice, with increasing frequency of global glomerular sclerosis and tubulointerstitial damage. On the other hand, although precise measurements of glomerular cell numbers also showed an apparent augmentation in both young and old RF/J mice compared to BALB/C mice, glomerular cellularity decreased with age in RF/J mice. Immunohistochemical study revealed massive immunoglobulin deposition from a young age in association with significantly higher accumulation of matrix proteins, such as types I and IV collagen and laminin from the early stage of life. In addition, in these glomeruli, transforming growth factor-beta 1 (TGF-beta 1) was highly expressed both in young and old mice. The mRNA expression of MMP-2 was up-regulated only in the early stage of life. Although PDGF mRNA of RF/J mice was significantly upregulated in the early stage of life, the differences between the mice disappeared in the late stage of life. Conclusions. These findings suggest that in RF/J mice, an immunopathological background inducing high serum immunoglobulin and IC levels from the early stage of life is closely related to mesangioproliferative glomerular lesions mediated by PDGF, and that development of massive extracellular matrixaccumulation in glomeruli was induced by up-regulated expression of TGF-beta with inappropriate regulation of protein turnover-related enzyme production.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:45:13