SMAD3 and SP1/SP3 Transcription Factors Collaborate to Regulate Connective Tissue Growth Factor Gene Expression in Myoblasts in Response to Transforming Growth Factor
SMAD3 and SP1/SP3 Transcription Factors Collaborate to Regulate Connective Tissue Growth Factor Gene Expression in Myoblasts in Response to Transforming Growth Factor
复制标题
DOI：
10.1002/jcb.25143
复制
发表时间：
2015-09-01
影响因子：
4
通讯作者：
Brandan, Enrique
中科院分区：
文献类型：
--
作者：
Cordova, Gonzalo;Rochard, Alice;Brandan, Enrique
纤维性疾病的特征是细胞外基质蛋白表达和沉积增加，Duchene肌营养不良症就是其中之一。在诱导纤维化的因素中，有转化生长因子-型(TGF-β)和基质细胞蛋白结缔组织生长因子(CTGF/CCN2)，后者是转化生长因子-1/SMAD信号通路的靶点，也是转化生长因子-β促纤维化作用的机制之一。CTGF和TGF在纤维化影响的组织中均有增加，但对转化生长因子-α在肌肉细胞中对CTGF表达的调控知之甚少。通过荧光素酶报告分析、定点突变和C2C12细胞中的特异性抑制物，我们描述了位于CTGF基因5个非编码区的一个新的SMAD结合元件(SBE)，它对转化生长因子介导的CTGF在成肌细胞中的表达起重要作用。此外，我们的研究结果表明，CTGF基因5‘端非编码区的额外转录因子结合位点(TFBS)对CTGF的表达具有重要作用，并且SP1/SP3因子参与了转化生长因子介导的CTGF表达。J.细胞。生物化学。116：1880-1887,2015。(C)2015年威利期刊公司。
Fibrotic disorders are characterized by an increase in extracellular matrix protein expression and deposition, Duchene Muscular Dystrophy being one of them. Among the factors that induce fibrosis are Transforming Growth Factor type (TGF-) and the matricellular protein Connective Tissue Growth Factor (CTGF/CCN2), the latter being a target of the TGF-/SMAD signaling pathway and is the responsible for the profibrotic effects of TGF-. Both CTGF and TGF are increased in tissues affected by fibrosis but little is known about the regulation of the expression of CTGF mediated by TGF- in muscle cells. By using luciferase reporter assays, site directed mutagenesis and specific inhibitors in C2C12 cells; we described a novel SMAD Binding Element (SBE) located in the 5 UTR region of the CTGF gene important for the TGF--mediated expression of CTGF in myoblasts. In addition, our results suggest that additional transcription factor binding sites (TFBS) present in the 5' UTR of the CTGF gene are important for this expression and that SP1/SP3 factors are involved in TGF--mediated CTGF expression. J. Cell. Biochem. 116: 1880-1887, 2015. (c) 2015 Wiley Periodicals, Inc.