Activation of connective tissue growth factor gene by the c-Maf and Lc-Maf transcription factors

概要

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The Maf family of transcription factors is expressed during development of variousorgans and tissues, and is involved in a variety of developmental and cellular differentiationprocesses. We previously found that c-maf and mafB are strongly expressed in hypertrophicchondrocytes during cartilage development. Connective tissue growth factor (CTGF) is alsoexpressed in hypertrophic chondrocytes. Adenovirus mediated introduction of c-maf gene intothe mouse fibroblast cell line C3H10T1/2 strongly induced CTGF expression. CTGF can beinduced by TGF-β via the SMAD pathway; however, the c-Maf could not induce TGF-β, norcould TGF-β induce the c-Maf, suggesting that activation of CTGF by Maf is TGF-βindependent. Reporter transfection analysis using C3H10T1/2 cells shows that c-Mafstimulates a CTGF reporter gene. Lc-Maf, a splice variant of c-Maf containing an extra 10amino acids in the carboxyl terminus, was a stronger inducer of the CTGF reporter gene thanc-Maf. Chromatin immunoprecipitation analysis showed that c-Maf binds to the promoterregion of the CTGF gene, indicating that Maf directly activates the CTGF gene. Gel mobilityshift assays indicated that c-Maf binds to the region near the transcription initiation site ofCTGF gene. Taken together, these data indicate that the CTGF gene is a target of c-Maf andLc-Maf in cartilage development.
Elsevier Inc.の論文
2005-12-05