Activation of connective tissue growth factor gene by the c-Maf and Lc-Maf transcription factors
Activation of connective tissue growth factor gene by the c-Maf and Lc-Maf transcription factors
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DOI：
10.1016/j.bbrc.2005.11.119
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发表时间：
2006-01-27
影响因子：
3.1
通讯作者：
Sakai, M
中科院分区：
文献类型：
--
作者：
Omoteyama, K;Ikeda, H;Sakai, M
Maf家族转录因子在各种器官和组织的发育过程中表达，并参与各种发育和细胞分化过程。我们以前发现，c-maf和mafB在软骨发育过程中的肥大软骨细胞中强烈表达。结缔组织生长因子（CTGF）也在肥大软骨细胞中表达。腺病毒介导的c-maf基因导入小鼠成纤维细胞系C3 H10 T1/2后，CTGF的表达明显增加。CTGF可由TGF-β通过SMAD途径诱导;然而，c-Maf不能诱导TGF-β，TGF-β也不能诱导c-Maf，表明Maf对CTGF的激活是TGF-β非依赖性的。使用C3 H10 T1/2细胞的报告基因转染分析表明，c-Maf刺激CTGF报告基因。Lc-Maf是c-Maf的剪接变体，在羧基末端含有额外的10个氨基酸，是比c-Maf更强的CTGF报告基因的诱导剂。染色质免疫沉淀分析表明，c-Maf结合到CTGF基因的启动子区，表明Maf直接激活CTGF基因。总之，这些数据表明CTGF基因是软骨发育中c-Maf和Lc-Maf的靶标。(c)2005年爱思唯尔公司All rights reserved.
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 immuno precipitation 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. (c) 2005 Elsevier Inc. All rights reserved.