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首页> 外文期刊>Cellular Signalling >Up-regulation of mouse mast cell protease-6 gene by transforming growth factor-beta and activin in mast cell progenitors
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Up-regulation of mouse mast cell protease-6 gene by transforming growth factor-beta and activin in mast cell progenitors

机译:通过转化生长因子-β和激活素在肥大细胞祖细胞中上调小鼠肥大细胞蛋白酶-6基因

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Previous studies have revealed that members of the transforming growth factor-beta (TGF-beta) including TGFbeta(1) and activin A modulate the function of mast cells. Here we show the up-regulation of mouse mast cell protease-6 (mMCP-6), which is expressed in differentiated mast cells, by TGF-beta(1) and activin A in bone marrow-derived cultured mast cell progenitors (BMCMCs). Quantitative real time RT-PCR analyses revealed that the mRNA level of mMCP-6 was slightly but reproducibly increased by treatment with TGF-beta(1) or activin A, which was regulated at the transcription level. Reporter assays showed that Smad3, a signal mediator of the TGF-beta/activin pathway, was responsible for the transcription. The TGF-beta response element is located at -153 bp relative to the transcription initiation site, CAGA. Microphthalmia-associated transcription factor (MITF), a tissue-specific transcription factor predominantly expressed in mast cells, melanocytes, the heart and skeletal muscle, also stimulated the transcription of mMCP-6. The region at -166 bp, GACCTG, was responsible for MITF-induced transcription. Mutations of the CAGA motif and the MITF responsive site indicated that the MITF site of mMCP-6 promoter is indispensable for the transcriptional activation by a constitutively active TGF-beta receptor (ALK5-TD), whereas the CAGA motif is dispensable for transcription by MITF. Transcriptional activation of mMCP-6 by the TGF-beta pathway was differently interacted with that by MITF isoform; ALK5-TD further enhanced MITF-E-induced transcription, whereas MITF-M-induced transcription abolished responsiveness to ALK5-TD. The positive regulation of mMCP-6 by the TGF-beta/activin pathway and the differential regulation by the MITF isoform suggest a rigorous regulation of mast cell function as effector cells of immune response. (C) 2004 Elsevier Inc. All rights reserved.
机译:先前的研究表明,包括TGFbeta(1)和激活素A在内的转化生长因子-beta(TGF-beta)成员可调节肥大细胞的功能。在这里,我们显示了小鼠肥大细胞蛋白酶-6(mMCP-6)的上调,在骨髓衍生的肥大细胞祖细胞(BMCMCs)中由TGF-beta(1)和激活素A在分化的肥大细胞中表达。实时定量RT-PCR分析显示,通过TGF-beta(1)或激活素A(在转录水平受到调控)的处理,mMCP-6的mRNA水平略有提高,但可再现地增加。记者分析表明,Smad3是TGF-β/激活素途径的信号介体,是转录的原因。 TGF-beta响应元件位于相对于转录起始位点CAGA的-153 bp处。小眼症相关转录因子(MITF)是一种主要在肥大细胞,黑素细胞,心脏和骨骼肌中表达的组织特异性转录因子,也刺激了mMCP-6的转录。 -166 bp的区域GACCTG负责MITF诱导的转录。 CAGA基序和MITF响应位点的突变表明,mMCP-6启动子的MITF位点对于组成型活性TGF-β受体(ALK5-TD)的转录激活是必不可少的,而CAGA基序对于MITF的转录是必不可少的。 TMC-β途径对mMCP-6的转录激活与MITF亚型的相互作用不同。 ALK5-TD进一步增强了MITF-E诱导的转录,而MITF-M诱导的转录消除了对ALK5-TD的响应。 TMC-β/激活素途径对mMCP-6的正调控和MITF同工型的差异调控表明肥大细胞功能作为免疫反应的效应细胞受到了严格的调控。 (C)2004 Elsevier Inc.保留所有权利。

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