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Original Paper

DOCA and TGF-β Induce Early Growth Response Gene-1 (Egr-1) Expression

Friedrich B.1 · Janessa A.1 · Artunc F.1 · Aicher W.K.2 · Müller G.A.3 · Lang F.4 · Risler T.1 · Alexander D.5

Author affiliations

1Department of Internal Medicine IV, University Hospital Tübingen2Department of Orthopedic Surgery, University Hospital Tübingen,3Departments of Nephrology and Rheumatology, University Hospital Göttingen,4Department of Physiology, University Tübingen,5Department of Oral and Maxillofacial Surgery, University Hospital Tübingen

Corresponding Author

Dr. Dorothea Alexander, PhD

Oral and Maxillofacial Surgery, University Hospital Tübingen

Osianderstr. 2-8, 72076 Tübingen (Germany)

Tel. +49-7071-2982418, Fax: +49-7071-29-5753

E-Mail dorothea.alexander@med.uni-tuebingen.de

Related Articles for ""

Cell Physiol Biochem 2008;22:465–474

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Renal fibrosis is characterized by excessive accumulation of extracellular matrix proteins. Recent findings show that transforming growth factor-β (TGF-β) induces a rapid but transient expression of early growth response gene-1 (Egr-1) by skin fibroblasts. The present study aims to define the role of Egr-1 in mineralocorticoid-induced renal fibrosis. Therefore, we transiently transfected immortalized human renal fibroblasts (TK188) with recombinant Egr-1 and analysed the transcription of several pro-fibrotic genes (Coll1A1, Coll1A2, osteopontin, TIMP-1, and CTGF). We also examined Egr-1 expression and the regulation of pro-fibrotic genes in DOCA- (deoxycorticosterone acetate) and TGF-β-treated renal fibroblasts. Finally, we compared Egr-1 gene expression in DOCA/high salt-induced fibrotic kidneys and untreated mice. Egr-1 transfection of TK188 fibroblasts induced the expression of TIMP-1 and osteopontin mRNA. Similar results were obtained after DOCA-activation of TK188 cells. Stimulation of TK188 with TGF-β, but not with DOCA, resulted in elevated Coll1A1/Coll1A2 and CTGF levels. Co-stimulation with DOCA and TGF-β was followed by enhanced Egr-1, Coll1A1, TIMP-1, and CTGF transcription. In conclusion, both DOCA and TGF-β alone or in combination synergistically induced Egr-1 expression by human renal fibroblasts. DOCA induction of TIMP-1/osteopontin is Egr-1 dependent, whereas TGF-β appears to induce Coll1A1 and CTGF by an Egr-1 independent pathway. In vivo analyses revealed significantly higher Egr-1 transcript levels in DOCA/high salt-induced fibrotic kidneys compared to untreated mice. Thus, we show for the first time that Egr-1 might participate in DOCA-induced renal fibrosis.

© 2008 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: July 14, 2008
Published online: December 09, 2008
Issue release date: December 2008

Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

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