Activation of connective tissue growth factor gene by the c-Maf and Lc-Maf transcription factors.
The Maf family of transcription factors is expressed during development of various organs and tissues, and is involved in a variety of developmental and cellular differentiation processes. We previously found that c-maf and mafB are strongly expressed in hypertrophic chondrocytes during cartilage development. Connective tissue growth factor (CTGF) is also expressed in hypertrophic chondrocytes. Adenovirus mediated introduction of c-maf gene into the mouse fibroblast cell line C3H10T1/2 strongly induced CTGF expression. CTGF can be induced by TGF-beta via the SMAD pathway; however, the c-Maf could not induce TGF-beta, nor could TGF-beta induce the c-Maf, suggesting that activation of CTGF by Maf is TGF-beta independent. Reporter transfection analysis using C3H10T1/2 cells shows that c-Maf stimulates a CTGF reporter gene. Lc-Maf, a splice variant of c-Maf containing an extra 10 amino acids in the carboxyl terminus, was a stronger inducer of the CTGF reporter gene than c-Maf. Chromatin immunoprecipitation analysis showed that c-Maf binds to the promoter region of the CTGF gene, indicating that Maf directly activates the CTGF gene. Taken together, these data indicate that the CTGF gene is a target of c-Maf and Lc-Maf in cartilage development.
Omoteyama
Kazuki
K
Department of Biochemistry, Graduate School of Medicine, Hokkaido University, N14, W7, Kita-ku, Sapporo 060-8638, Japan.
Ikeda
Hiromi
H
Imaki
Junko
J
Sakai
Masaharu
M
D000818:Animals; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D017874:Immediate-Early Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D011401:Promoter Regions, Genetic; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology
C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D014157:Transcription Factors; D055513:Connective Tissue Growth Factor