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 β1 (TGF-β1) translation. However, the upstream regulators and mechanism of P311 gene regulation remain unclear, although we previously found that cytokines, hypoxia, and TGF-β1 could upregulate P311 transcription. Here, we aimed to elucidate the molecular mechanism of TGF-β1-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-β1, 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.

中文翻译：

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间充质同源盒1转化纤维化中生长因子β1诱导的P311基因转录的分子机制。

器官纤维化的特征是过量的成纤维细胞，并且尚未充分阐明细胞外基质和分子基础。最近的研究证明，P311是一种8 kDa的保守蛋白，可以部分上调转化生长因子β1（TGF-β1）的翻译，从而促进皮肤，肾脏，肝脏和肺等各种器官纤维化。然而，尽管我们先前发现细胞因子，低氧和TGF-β1可以上调P311转录，但上游调节剂和P311基因调节的机制仍不清楚。在这里，我们旨在阐明TGF-β1诱导的P311转录调控的分子机制，重点是间充质同源盒1（Meox1）。在本文中，我们通过生物信息学分析和荧光素酶报告基因分析鉴定了P311的核心启动子。此外，我们证明了Meox1 TGF-β1诱导的TGF-β1可以与P311的启动子结合并促进其转录活性。此外，Meox1对P311转录表达的影响有助于改变人类皮肤成纤维细胞的迁移和增殖。总之，我们确定Meox1是P311基因的新型转录因子，为纤维化的发病机理提供了新线索。