Endometrial stromal cell proteomic analysis reveals LIM and SH3 protein I (LASPI) plays important roles in the progression of adenomyosis
Endometrial stromal cell proteomic analysis reveals LIM and SH3 protein I (LASPI) plays important roles in the progression of adenomyosis
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DOI：
10.1093/molehr/gaab008
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发表时间：
2021-02-05
影响因子：
4
通讯作者：
Zou, Yang
中科院分区：
文献类型：
--
作者：
Liu, Faying;Li, Zengming;Zou, Yang
子宫腺肌病是最常见的妇科疾病之一，其发病机制的分子生物学事件尚未完全了解。以往的研究表明，子宫内膜间质细胞（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，我们利用双向凝胶电泳结合蛋白质鉴定质谱（2D/MS）蛋白质组学分析，比较差异蛋白质表达谱之间的配对在位和异位胚胎干细胞（EuESCs和EcESCs在子宫腺肌病，共32个显着改变的蛋白质点被确定。其中，LIM和SH 3蛋白I（LASPI）在EcESCs中的表达较EuESCs明显增加。免疫组化结果显示，LASPI在异位子宫内膜间质细胞中的表达高于在位子宫内膜;进一步的功能分析显示，LASPI过表达可促进EcESCs的增殖、迁移和侵袭。此外，我们还发现LASPI在EcESCs中的表达失调与LASPI基因启动子区的DNA超甲基化有关。然而，LASPI在子宫腺肌病中上调引起的细胞增殖、侵袭和迁移增强的详细分子机制需要进一步研究。我们的数据首次表明LASPI在子宫腺肌病的发病机制中起重要作用，并可作为子宫腺肌病的预后生物标志物。
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 I (LASPI) was increased significantly in EcESCs compared to EuESCs. Immunohistochemical assay showed that LASPI was overexpressed in the stromal cells of ectopic endometriums compared to eutopic endometriums; further functional analyses revealed that LASPI overexpression could enhance cell proliferation, migration and invasion of EcESCs. Furthermore, we also showed that the dysregulated expression of LASPI in EcESCs was associated with DNA hypermethylation in the promoter region of the LASPI gene. However, the detailed molecular mechanisms of enhancing cell proliferation, invasion and migration caused by upregulated LASPI in adenomyosis needs further study. For the first time, our data suggested that LASPI plays important roles in the pathogenesis of adenomyosis, and could serve as a prognostic biomarker of adenomyosis.