Molecular Mechanism of Mesenchyme Homeobox 1 in Transforming Growth Factor beta 1-Induced P311 Gene Transcription in Fibrosis
Molecular Mechanism of Mesenchyme Homeobox 1 in Transforming Growth Factor beta 1-Induced P311 Gene Transcription in Fibrosis
复制标题
间质同源盒1在转化生长因子β1诱导的纤维化P311基因转录中的分子机制
DOI：
10.3389/fmolb.2020.00059
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发表时间：
2020-04-28
影响因子：
5
通讯作者：
Luo, Gaoxing
中科院分区：
文献类型：
--
作者：
Wei, Zhiyuan;Han, Chao;Luo, Gaoxing
器官纤维化的特点是纤维母细胞过多，细胞外基质和分子基础尚未完全阐明。最近的研究表明，P311，一个8-kDa的保守蛋白，可以促进各种器官的纤维化，如皮肤，肾脏，肝脏和肺，部分通过上调转化生长因子β 1（TGF-β 1）的翻译。然而，P311基因调控的上游调控因子和机制尚不清楚，尽管我们先前发现细胞因子、缺氧和TGF-β 1可以上调P311的转录。在这里，我们的目的是阐明TGF-β 1诱导的P311转录调控的分子机制，重点是间充质同源框1（Meox 1）。本文通过生物信息学分析和荧光素酶报告基因分析，对P311基因的核心启动子进行了鉴定。此外，我们证明了TGF-β 1诱导的Meox 1可以与P311的启动子结合并促进其转录活性。此外，Meox 1对P311转录表达的影响有助于改变人真皮成纤维细胞的迁移和增殖。结论：Meox 1是P311基因的一个新的转录因子，为研究P311在肝纤维化中的作用机制提供了新的线索。
Organ fibrosis is characterized by excessive fibroblast, and extracellular matrix and the molecular basis are not fully elucidated. Recent studies have proven that P311, an 8-kDa conserved protein, could promote various organ fibrosis, such as skin, kidney, liver, and lung, partially through upregulating transforming growth factor beta 1 (TGF-beta 1) translation. However, the upstream regulators and mechanism of P311 gene regulation remain unclear, although we previously found that cytokines, hypoxia, and TGF-beta 1 could upregulate P311 transcription. Here, we aimed to elucidate the molecular mechanism of TGF-beta 1-induced P311 transcriptional regulation, focusing on mesenchyme homeobox 1 (Meox1). In this article, we identified the core promoter of P311 through bioinformatics analysis and luciferase reporter assays. Moreover, we demonstrated that Meox1, induced by TGF-beta 1, could bind to the promoter of P311 and promote its transcriptional activity. Furthermore, the effect of Meox1 on P311 transcriptional expression contributed to altered migration and proliferation in human dermal fibroblast cells. In conclusion, we identified Meox1 as a novel transcription factor of P311 gene, providing a new clue of the pathogenesis in fibrosis.