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羧肽酶抑制剂 LXN 在子宫内膜组织中的表达随月经周期变化,在子宫内膜异位症病变中上调。

Carboxypeptidase Inhibitor LXN Expression in Endometrial Tissue Is Menstrual Cycle Phase-Dependent and Is Upregulated in Endometriotic Lesions.

机构信息

Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia.

Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, and Karolinska University Hospital, 17177 Stockholm, Sweden.

出版信息

Genes (Basel). 2024 Aug 17;15(8):1086. doi: 10.3390/genes15081086.

DOI:10.3390/genes15081086
PMID:39202445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11353285/
Abstract

Endometriosis is a chronic hormone-dependent disease characterized by the spread of endometrial cells outside the uterus, which form endometriotic lesions and disrupt the functions of the affected organs. The etiopathogenesis of endometriosis is still unclear, and thus it is important to examine the genes that may contribute to the establishment of endometriotic lesions. The aim of this study was to investigate the expression of new potential candidate gene (), an inhibitor of carboxypeptidases, in endometrium and endometriotic lesions to elucidate its possible role in endometriosis development. expression in tissues was assessed using quantitative reverse transcription PCR (qRT-PCR) analysis and immunohistochemical staining (IHC). The functions of were examined using Transwell and MTT assays. qRT-PCR analysis revealed that expression in endometrium was menstrual cycle-dependent, being lowest in the early-secretory phase and highest in the late-secretory phase and was significantly upregulated in endometriotic lesions. IHC confirmed LXN expression in endometrial stromal cells, and in vitro assays demonstrated that knockdown of LXN effectively reduced the migratory capacity of endometrial stromal cells while promoting cell viability. In conclusion, our results showed that LXN can be involved in the pathogenesis of endometriosis by regulating the proliferation and migration activity of endometriotic stromal cells.

摘要

子宫内膜异位症是一种慢性激素依赖性疾病,其特征是子宫内膜细胞在子宫外扩散,形成子宫内膜异位病变,并破坏受影响器官的功能。子宫内膜异位症的病因发病机制尚不清楚,因此检查可能有助于建立子宫内膜异位病变的基因很重要。本研究旨在研究新的潜在候选基因(),一种羧肽酶抑制剂,在子宫内膜和子宫内膜异位病变中的表达,以阐明其在子宫内膜异位症发展中的可能作用。使用定量逆转录 PCR(qRT-PCR)分析和免疫组织化学染色(IHC)评估组织中的表达。使用 Transwell 和 MTT 测定法检查的功能。qRT-PCR 分析显示,子宫内膜中表达呈月经周期依赖性,在早期分泌期最低,在晚期分泌期最高,在子宫内膜异位病变中显著上调。IHC 证实 LXN 在子宫内膜基质细胞中的表达,体外实验表明 LXN 敲低可有效降低子宫内膜基质细胞的迁移能力,同时促进细胞活力。总之,我们的研究结果表明,LXN 可通过调节子宫内膜异位症基质细胞的增殖和迁移活性参与子宫内膜异位症的发病机制。

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Anal Chim Acta. 2023 Dec 15;1284:341993. doi: 10.1016/j.aca.2023.341993. Epub 2023 Nov 3.
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LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells.LXN 缺乏通过促进血管内皮细胞中 Filamin A 的蛋白水解切割来调节细胞骨架重塑。
J Cell Mol Med. 2021 Jul;25(14):6815-6827. doi: 10.1111/jcmm.16685. Epub 2021 Jun 3.
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In Depth Quantitative Proteomic and Transcriptomic Characterization of Human Adipocyte Differentiation using the SGBS Cell Line.
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Proteomics. 2020 Aug;20(15-16):e1900405. doi: 10.1002/pmic.201900405.
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Uterine Fluid Proteins for Minimally Invasive Assessment of Endometrial Receptivity.用于微创评估子宫内膜容受性的子宫液蛋白质。
J Clin Endocrinol Metab. 2020 Jan 1;105(1). doi: 10.1210/clinem/dgz019.
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A molecular tool for menstrual cycle phase dating of endometrial samples in endometriosis transcriptome studies†.一种用于子宫内膜异位症转录组研究中子宫内膜样本月经周期阶段测定的分子工具†
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