Liraglutide ameliorates intrauterine adhesion by inhibiting NF-κb phosphorylation and reducing epithelial-mesenchymal transition

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Jie Shi , Weicong Xu , Tao Yang , Ayana Bayijuma , Yujie Huang , Yunxiao Zhou
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引用次数: 0

Abstract

Background

Intrauterine adhesions (IUA) seriously affect female reproductive function, but the clinical treatment effect is not good. Semaglutide and Dulaglutide, receptor agonists of the gastrointestinal hormone GLP-1, have been reported to alleviate IUA. We sought to determine whether liraglutide, also a GLP-1 receptor agonist, would exert a protective effect and explore the underlying mechanism.

Methods

The IUA rat models were conducted via the mechanical damage method and rats were administrated with liraglutide. The inflammation and collagen fibrosis were evaluated via hematoxylin-eosin and Masson staining. The content of E-cadherin and N-cadherin was measured by immunohistochemistry, immunofluorescence, and Western blot. To stimulate IUA, human endometrial organoids were treated with RU486, and primary human endometrial epithelial cells were treated with TGF-β. SuperPred analysis was to predict the potential targets of liraglutide, with cellular thermal shift assay to detect its interaction with NF-κb.

Results

Liraglutide treatment reduced endometrial inflammation, collagen fibrosis, and EMT in IUA rats as well as human organoid IUA models. NF-κb phosphorylation was up-regulated in the IUA model group and was reversed by liraglutide treatment. Database predictions suggested that NF-κb may be a predicted direct target of liraglutide and our results confirmed that. Further results showed that in human endometrial organoids, interfering with the targeting of NF-κB by liraglutide attenuated the effects of liraglutide on inflammation, fibrosis, and EMT in the IUA models.

Conclusions

Liraglutide reduces EMT by directly targeting NF-κb and inhibiting NF-κb phosphorylation, thereby improving IUA.
利拉鲁肽通过抑制NF-κb磷酸化和减少上皮-间质转化改善宫内粘连。
背景:宫腔粘连严重影响女性生殖功能,但临床治疗效果不佳。胃肠道激素GLP-1的受体激动剂Semaglutide和Dulaglutide已被报道可缓解IUA。我们试图确定利拉鲁肽,也是一种GLP-1受体激动剂,是否会发挥保护作用并探索潜在的机制。方法:采用机械损伤法建立IUA大鼠模型,利拉鲁肽给药。苏木精-伊红染色、马松染色评价炎症及胶原纤维化。采用免疫组织化学、免疫荧光和western blot检测E-cadherin和N-cadherin的含量。为了刺激IUA,我们用RU486处理人子宫内膜类器官,用TGF-β处理人子宫内膜上皮细胞。SuperPred分析预测利拉鲁肽的潜在靶点,并用细胞热移法检测其与NF-κb的相互作用。结果:利拉鲁肽治疗可减轻IUA大鼠和人类器官IUA模型的子宫内膜炎症、胶原纤维化和EMT。IUA模型组小鼠NF-κb磷酸化水平上调,利拉鲁肽使其磷酸化水平逆转。数据库预测表明NF-κb可能是利拉鲁肽预测的直接靶点,我们的结果证实了这一点。进一步的研究结果表明,在人子宫内膜类器官中,干扰利拉鲁肽对NF-κB的靶向可减弱利拉鲁肽对IUA模型中炎症、纤维化和EMT的作用。结论:利拉鲁肽通过直接靶向NF-κb,抑制NF-κb磷酸化来降低EMT,从而改善IUA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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