Involvement of Transcription Factor 21 in the Pathogenesis of Fibrosis in Endometriosis
Involvement of Transcription Factor 21 in the Pathogenesis of Fibrosis in Endometriosis
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DOI：
10.1016/j.ajpath.2019.09.008
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发表时间：
2020-01-01
影响因子：
6
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
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作者：
Ganieva, Umida;Nakamura, Tomoko;Kikkawa, Fumitaka
反复的组织损伤和修复以及纤维化在子宫内膜异位症中起着关键作用。纤维化组织由细胞外基质蛋白组成，受促进细胞增殖和存活的转录因子调节。骨膜蛋白是一种重要的细胞外基质蛋白。本研究的目的是确定转录因子21（TCF 21）是否参与子宫内膜异位症的发展作为骨膜蛋白的上游调控基因。分析福尔马林固定、石蜡包埋的组织样本[无子宫内膜异位症女性的正常子宫内膜;子宫内膜异位症女性的在位子宫内膜;卵巢子宫内膜异位症（OE）;和深部浸润性子宫内膜异位症（DIE）]和相应的细胞。基础，短暂刺激，并敲低骨膜蛋白和TCF 21浓度的基质细胞的妇女或没有子宫内膜异位症进行了检查。Periostin和TCF 21在正常子宫内膜中无表达，在子宫内膜异位症在位内膜中弱阳性表达，在OE中中度阳性表达，在DIE中强阳性表达。2型辅助性T细胞因子（IL-4、IL-13和转化生长因子-β 1）增加了骨膜蛋白和TCF 21的mRNA表达。这些细胞因子骨膜蛋白和TCF 21共定位于OE和DIE的基质中。针对人TCF 21基因的siRNA抑制骨膜蛋白的表达。将TCF 21质粒载体转染到没有子宫内膜异位症的妇女的基质细胞中，其最初既不表达骨膜蛋白也不表达TCF 21，导致TCF 21和骨膜蛋白表达。TCF 21和periostin参与调节子宫内膜异位症的纤维化。TCF 21可能成为子宫内膜异位症治疗的靶点和生物标志物。
Repeated tissue injury and repair and fibrosis play a pivotal role in endometriosis. Fibrotic tissue consists of extracellular matrix proteins, regulated by transcriptional factors promoting cell proliferation and survival. Periostin is one of the putative key extracellular matrix proteins. This study aimed to determine whether transcription factor 21 (TCF21) is involved in the development of endometriosis as an upstream regulatory gene of periostin. Formalin-fixed, paraffin-embedded tissue samples [normal endometrium of women without endometriosis; eutopic endometrium of women with endometriosis; ovarian endometriosis (OE); and deep infiltrating endometriosis (DIE)] and respective cells were analyzed. Basal, transiently stimulated, and knocked down periostin and TCF21 concentrations in stromal cells of women with or without endometriosis were examined. Periostin and TCF21 expressions were undetected in normal endometrium of women without endometriosis, weakly positive in eutopic endometrium of women with endometriosis, moderately positive in OE, and strongly positive in DIE. Type 2 helper T-cell cytokines (IL-4, IL-13, and transforming growth factor-beta 1) increased the mRNA expression of periostin and TCF21. These cytokines, periostin, and TCF21 colocalized in the stroma of OE and DIE. siRNA against human TCF21 gene suppressed periostin expression. Transfection of TCF21 plasmid vector into stromal cells of women without endometriosis, which originally expressed neither periostin nor TCF21, resulted in TCF21 and periostin expression. TCF21 and periostin are involved in the regulation of fibrosis in endometriosis. TCF21 may be a promising therapeutic target and biomarker in endometriosis.