Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Mol Hum Reprod. 2021 Feb 27;27(3). doi: 10.1093/molehr/gaab008.
Adenomyosis is one of the most common gynecological disorders that the molecular events underlying its pathogenesis remain not fully understood. Prior studies have shown that endometrial stromal cells (ESCs) played crucial roles in the pathogenesis of adenomyosis. In this study, we utilized two-dimensional gel electrophoresis combined with protein identification by mass spectrometry (2D/MS) proteomics analysis to compare the differential protein expression profile between the paired eutopic and ectopic ESCs (EuESCs and EcESCs) in adenomyosis, and a total of 32 significantly altered protein spots were identified. Among which, the expression of LIM and SH3 protein 1 (LASP1) was increased significantly in EcESCs compared to EuESCs. Immunohistochemical assay showed that LASP1 was overexpressed in the stromal cells of ectopic endometriums compared to eutopic endometriums; further functional analyses revealed that LASP1 overexpression could enhance cell proliferation, migration and invasion of EcESCs. Furthermore, we also showed that the dysregulated expression of LASP1 in EcESCs was associated with DNA hypermethylation in the promoter region of the LASP1 gene. However, the detailed molecular mechanisms of enhancing cell proliferation, invasion and migration caused by upregulated LASP1 in adenomyosis needs further study. For the first time, our data suggested that LASP1 plays important roles in the pathogenesis of adenomyosis, and could serve as a prognostic biomarker of adenomyosis.
子宫腺肌病是最常见的妇科疾病之一,但其发病机制的分子事件仍不完全清楚。先前的研究表明,子宫内膜基质细胞(ESCs)在子宫腺肌病的发病机制中起着至关重要的作用。在这项研究中,我们利用二维凝胶电泳结合质谱(2D/MS)蛋白质组学分析比较了配对的在位和异位子宫内膜基质细胞(EuESCs 和 EcESCs)在子宫腺肌病中的差异蛋白表达谱,共鉴定出 32 个明显改变的蛋白点。其中,LIM 和 SH3 蛋白 1(LASP1)在 EcESCs 中的表达明显高于 EuESCs。免疫组织化学检测显示,LASP1 在异位子宫内膜的基质细胞中过度表达,而在在位子宫内膜中则表达较低;进一步的功能分析表明,LASP1 的过表达可以增强 EcESCs 的细胞增殖、迁移和侵袭能力。此外,我们还表明,EcESCs 中 LASP1 的失调表达与 LASP1 基因启动子区域的 DNA 超甲基化有关。然而,上调的 LASP1 在子宫腺肌病中引起细胞增殖、侵袭和迁移增强的详细分子机制还需要进一步研究。我们的数据首次表明,LASP1 在子宫腺肌病的发病机制中起着重要作用,可作为子宫腺肌病的预后标志物。