title: Kinetics of connective tissue growth factor expression during experimental proliferative glomerulonephritis.
abstract: Connective tissue growth factor (CTGF) is a member of the CCN family of immediate early genes, which are involved in cell proliferation, migration, and matrix production. Recently, CTGF was observed to be strongly upregulated in human proliferative and fibrogenic renal disease. By in situ hybridization and reverse transcriptase-PCR, the expression of CTGF was investigated in experimental proliferative glomerulonephritis induced by injection of anti-Thy-1.1 antibody in the rat. CTGF expression in cultured rat mesangial cells and glomerular visceral epithelial cells (GVEC) was studied in response to transforming growth factor beta (TGF-beta), an essential pathogenetic factor in this model. In normal rat kidneys, only some GVEC expressed CTGF mRNA. In anti-Thy-1.1 nephritis, CTGF mRNA expression was strongly increased in extracapillary and mesangial proliferative lesions and in areas of periglomerular fibrosis. Early glomerular CTGF overexpression in GVEC coincided with a striking upregulation of TGF-beta2 and to a lesser extent of TGF-beta3. Glomerular CTGF mRNA expression was maximal at day 7, in association with increased TGF-beta1 mRNA and protein expression. CTGF mRNA overexpression by parietal epithelial cells preceded the periglomerular appearance of alpha-smooth muscle actin-positive fibroblasts. In cultured mesangial cells, TGF-beta1, -beta2, and -beta3 transiently increased the CTGF/glyceraldehyde phosphate dehydrogenase mRNA ratio up to threefold versus control at 4 h. In GVEC, upregulation of CTGF mRNA by these TGF-beta isoforms was more sustained, being 8- to 16-fold versus control at 24 h. The kinetics of CTGF expression strongly suggest a role in glomerular repair, possibly downstream of TGF-beta, in this model of transient renal injury.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Internal Medicine, Chubu Rousai Hospital, Nagoya, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Pathology University of Utrecht, Utrecht, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bende
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M Anwar
authors.initials: MA
authors.lastname: Chand
authors.affiliation: Department of Nephrology, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Livio
authors.initials: L
authors.lastname: Kleij
authors.affiliation: Department of Nephrology, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Weening
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Aten
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005921:Glomerulonephritis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D017931:DNA Primers; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor