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子宫内膜异位症病灶中高水平的一组综合基质金属蛋白酶:验证细胞衰老在子宫内膜异位症发病机制中的关键作用

High levels of a comprehensive set of matrix metalloproteinases in endometriotic lesions: validating the key role of cellular senescence in endometriosis pathogenesis.

作者信息

Palmieri Laura, Malvezzi Helena, Azevedo Bruna Cestari de, Placencia Eduardo Varejão Díaz, Antonioli Eliane, Podgaec Sérgio

机构信息

Academic, Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.

Researcher, Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.

出版信息

Einstein (Sao Paulo). 2025 Aug 18;23:eAO1345. doi: 10.31744/einstein_journal/2025AO1345. eCollection 2025.

DOI:10.31744/einstein_journal/2025AO1345
PMID:40834152
Abstract

BACKGROUND

This study reveals elevated levels of MMP-1, MMP-2, and MMP-3 in endometriotic lesions, potentially reflecting a senescenceassociated secretory phenotype. No corresponding increase was observed in peritoneal fluid, possibly due to technical or sample-related limitations. These findings support the potential of MMPs as biomarkers and therapeutic targets in endometriosis.

BACKGROUND

MMP-1, MMP-2, and MMP-3 are upregulated in endometriotic lesions.

BACKGROUND

The study findings suggest a senescence-associted secretory phenotype in endometriosis.

BACKGROUND

The study findings support targeting senescence pathways in endometriosis.

OBJECTIVE

To investigate the roles of cellular senescence and dysfunctional extracellular matrix metalloproteinases (MMPs) in perpetuating chronic inflammation and facilitating the establishment of endometriotic lesions. By analyzing the MMP activity in the endometrial tissue and peritoneal fluid, we aimed to obtain novel insights into the molecular mechanisms underlying endometriosis-related pathophysiology.

METHODS

The endometrial tissue and peritoneal fluid samples were collected laparoscopically from 12 women with endometriosis and 16 healthy controls. Gelatin zymography was performed to assess the activity of MMP-2, and multiplex assays were performed to determine the concentrations of MMP-1 and MMP-3 proteins. Statistical analyses were performed using Generalized Linear Models (GzLM) and SPSS software.

RESULTS

Gelatin zymography revealed higher pro-MMP-2 activity in endometriotic lesions than in eutopic and control endometrium. However, no differences were observed in peritoneal fluid samples. Additionally, MMP-1 and MMP-3 protein levels were elevated in endometriotic lesions compared with those in the eutopic endometrium, whereas only MMP-3 was increased compared with that in the control. No statistical significance was observed for MMP-2, MMP-1, and MMP-3 in the peritoneal fluid samples.

CONCLUSION

Increased levels of MMP-1, MMP-2, and MMP-3 in endometriotic lesions indicate that endometriosis may have a unique metabolomic signature linked to cell cycle arrest and inflammation. This may contribute to the pathogenesis of endometriosis by facilitating implantation of ectopic endometrium-like tissue in a disturbed immune environment.

摘要

背景

本研究揭示了子宫内膜异位症病灶中基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-3(MMP-3)水平升高,这可能反映了一种与衰老相关的分泌表型。在腹腔液中未观察到相应升高,可能是由于技术或样本相关的局限性。这些发现支持了基质金属蛋白酶作为子宫内膜异位症生物标志物和治疗靶点的潜力。

背景

MMP-1、MMP-2和MMP-3在子宫内膜异位症病灶中上调。

背景

研究结果提示子宫内膜异位症存在一种与衰老相关的分泌表型。

背景

研究结果支持针对子宫内膜异位症衰老途径进行治疗。

目的

探讨细胞衰老和功能失调的细胞外基质金属蛋白酶(MMPs)在维持慢性炎症和促进子宫内膜异位症病灶形成中的作用。通过分析子宫内膜组织和腹腔液中的MMP活性,我们旨在深入了解子宫内膜异位症相关病理生理学的分子机制。

方法

通过腹腔镜从12例子宫内膜异位症患者和16例健康对照者中采集子宫内膜组织和腹腔液样本。采用明胶酶谱法评估MMP-2的活性,采用多重分析法测定MMP-1和MMP-3蛋白的浓度。使用广义线性模型(GzLM)和SPSS软件进行统计分析。

结果

明胶酶谱显示,子宫内膜异位症病灶中前MMP-2活性高于在位内膜和对照内膜。然而,腹腔液样本中未观察到差异。此外,与在位内膜相比,子宫内膜异位症病灶中MMP-1和MMP-3蛋白水平升高,而与对照相比仅MMP-3升高。腹腔液样本中MMP-2、MMP-1和MMP-3无统计学意义。

结论

子宫内膜异位症病灶中MMP-1、MMP-2和MMP-3水平升高表明,子宫内膜异位症可能具有与细胞周期停滞和炎症相关的独特代谢组学特征。这可能通过在紊乱的免疫环境中促进异位子宫内膜样组织的植入而导致子宫内膜异位症的发病机制。

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