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子宫内膜异位症病灶中较高的纤维化含量与前列腺素E2信号传导减弱有关。

Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling.

作者信息

Huang Qingqing, Liu Xishi, Guo Sun-Wei

机构信息

Shanghai OB/GYN Hospital Fudan University Shanghai China.

The Third Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong China.

出版信息

Reprod Med Biol. 2021 Nov 1;21(1):e12423. doi: 10.1002/rmb2.12423. eCollection 2022 Jan.

DOI:10.1002/rmb2.12423
PMID:34938147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8656679/
Abstract

PURPOSE

While the prevailing view holds that the prostaglandin E2 (PGE) signaling plays a vital role in endometriosis, PGE also is known to be anti-fibrotic. We investigated the immunostaining of COX-2, EP2, and EP4, along with fibrotic content in ovarian endometrioma (OE) and deep endometriosis (DE) lesions, and in OE lesions from adolescent and adult patients. In addition, we evaluated the effect of substrate stiffness on the expression of COX-2, EP2, and EP4 in endometrial stromal cells.

METHODS

Immunohistochemistry analysis of COX-2, EP2, and EP4, along with the quantification of lesional fibrosis, was conducted for OE and DE lesion samples and also OE lesion samples from adolescent and adult patients. The effect of substrate rigidity on fibroblast-to-myofibroblast transdifferentiation (FMT) and the expression of COX-2, EP2, and EP4, with or without TGF-β1 stimulation, were investigated.

RESULTS

The immunostaining of COX-2, EP2, and EP4 was substantially reduced in endometriotic lesions as lesions became more fibrotic. Both TGF-β1 stimulation and stiff substrates induced FMT and reduced the expression of COX-2, EP2, and EP4.

CONCLUSIONS

Since fibrosis is a common feature of endometriosis, our results thus cast doubts on the use of therapeutics that suppresses the PGE signaling pathway, either by inhibiting COX-2 or EP2/EP4.

摘要

目的

虽然普遍观点认为前列腺素E2（PGE）信号传导在子宫内膜异位症中起重要作用，但PGE也已知具有抗纤维化作用。我们研究了环氧化酶-2（COX-2）、前列腺素E2受体亚型2（EP2）和前列腺素E2受体亚型4（EP4）的免疫染色，以及卵巢子宫内膜异位囊肿（OE）和深部子宫内膜异位症（DE）病变中，以及青少年和成年患者的OE病变中的纤维化含量。此外，我们评估了底物硬度对子宫内膜基质细胞中COX-2、EP2和EP4表达的影响。

方法

对OE和DE病变样本以及青少年和成年患者的OE病变样本进行COX-2、EP2和EP4的免疫组织化学分析，以及病变纤维化的定量分析。研究了底物硬度对成纤维细胞向肌成纤维细胞转分化（FMT）以及COX-2、EP2和EP4表达的影响，有无转化生长因子-β1（TGF-β1）刺激。

结果

随着子宫内膜异位症病变纤维化程度增加，COX-2、EP2和EP4的免疫染色显著降低。TGF-β1刺激和硬底物均诱导FMT并降低COX-2、EP2和EP4的表达。

结论

由于纤维化是子宫内膜异位症的一个共同特征，因此我们的结果对通过抑制COX-2或EP2/EP4来抑制PGE信号通路的治疗方法的使用提出了质疑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/36a96879d754/RMB2-21-e12423-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/4aafc8cb9369/RMB2-21-e12423-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/0044791b255f/RMB2-21-e12423-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/6977e074c54d/RMB2-21-e12423-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/36a96879d754/RMB2-21-e12423-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/4aafc8cb9369/RMB2-21-e12423-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/0044791b255f/RMB2-21-e12423-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/6977e074c54d/RMB2-21-e12423-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/8656679/36a96879d754/RMB2-21-e12423-g003.jpg

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