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CTGF expression in mesangial cells: Involvement of SMADs, MAP kinase, and PKC

Chen, YJ; Blom, IE; Sa, S; Goldschmeding, R; Abraham, DJ; Leask, A; (2002) CTGF expression in mesangial cells: Involvement of SMADs, MAP kinase, and PKC. KIDNEY INT , 62 (4) 1149 - 1159.

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Abstract

Background. The induction of excess matrix in renal fibrosis seems to be mediated, at least in part, by the transforming growth factor-beta (TGF-beta)-mediated induction of connective tissue growth factor (CTGF) in mesangial cells.Methods. By examining CTGF protein and mRNA expression and promoter activity in the presence or absence of TGF-beta or inhibitors, the signaling pathways controlling basal and TGF-beta-induced CTGF expression in mesangial cells were investigated.Results. TGF-beta enhances CTGF mRNA and protein expression in mesangial cells. Mutation of a consensus SMAD binding element in the CTGF promoter completely abolished TGF-beta-induced CTGF expression and reduced basal CTGF expression. The previously identified basal control element-1 (BCE-1) site, but not Sp1 contributes to basal CTGF promoter activity. Ras/MEK/ERK, protein kinase C (PKC) and tyrosine kinase activity also contribute to basal and TGF-beta-induced CTGF promoter activity in cultured mesangial cells.Conclusions. The TGF-beta-induction of CTGF in mesangial cells requires SMADs and PKC/ras/MEK/ERK pathways. SMADs are involved in basal CTGF expression, which presumably reflects the fact that mesangial cells express TGF-beta endogenously. TGF-beta also induces CTGF through ras/MEK/ERK. Inhibiting ras/MEK/ERK seems not to reduce phosphorylation (that is, activation) of SMADs, suggesting that SMADs, although necessary, are insufficient for the TGF-beta-stimulation of the CTGF promoter through ras/MEK/ERK. Thus, maximal TGF-beta induction of CTGF requires synergy between SMAD and ras/MEK/ERK signaling.

Type: Article
Title: CTGF expression in mesangial cells: Involvement of SMADs, MAP kinase, and PKC
Keywords: connective tissue growth factor, gene regulation, kidney fibrosis, SMADs, mitogen activated protein kinase, protein kinase C, wound healing, TISSUE GROWTH-FACTOR, ACTIVATED PROTEIN-KINASES, FACTOR-BETA, DIABETIC-NEPHROPATHY, TGF-BETA, GENE-EXPRESSION, SCLERODERMA FIBROBLASTS, COLLAGEN EXPRESSION, EPITHELIAL-CELLS, RESPONSE ELEMENT
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/119996
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