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胃饥饿素作为慢性炎症性疾病治疗靶点的潜力:来自人子宫内膜基质细胞的证据。

Ghrelin's potential as a therapeutic target for chronic inflammatory diseases: evidence from human endometrial stromal cells.

作者信息

Dong Wenhui, Mu Hongkai, Jia Fan, Wei Yingying, Lv JingJing, Zhou Shizhao, Yu Shiping, Liang Tingting

机构信息

Medical Imaging Department, Shanxi Medical University, Taiyuan, China.

Department of Interventional Therapy, Second Hospital of Shanxi Medical University, Taiyuan, China.

出版信息

Front Endocrinol (Lausanne). 2025 Sep 1;16:1587490. doi: 10.3389/fendo.2025.1587490. eCollection 2025.

DOI:10.3389/fendo.2025.1587490
PMID:40958911
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12433839/
Abstract

BACKGROUND

Ghrelin, a peptide composed of 28 amino acids, is recognized for its role in regulating appetite and energy balance. Recently, it has also been identified as an immunomodulator that could significantly influence immune responses in chronic inflammatory conditions. The role of ghrelin on cell viability and cytokine expression is presented here for human endometrial stromal (hEM15A) cells, with attention to the way this peptide could modulate inflammation.

METHODS

In this study, the hEM15A cells were cultured and treated with Ghrelin at concentrations ranging from 1 μM to 1000 μM. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Levels of the cytokines TNF-α, IL-6, and IL-10 were measured by ELISA, and the expression of the Ghrelin receptor was confirmed through Western blot (WB) analysis.

RESULTS

The results demonstrated successful expression of the Ghrelin receptor (GHSR) in hEM15A cells. Analysis of cell viability indicated that Ghrelin positively affected cell proliferation, particularly at higher concentrations. ELISA results showed a significant decrease in pro-inflammatory cytokines TNF-α and IL-6, coupled with a notable increase in the anti-inflammatory cytokine IL-10, in a dose-dependent manner.

CONCLUSION

Ghrelin can exert its effects through its receptor GHSR. Meanwhile, Ghrelin stimulates cell growth without causing decrease in viability; it has cell protective effect by regulating inflammation at the molecular level by balancing the release of some key pro-inflammatory cytokines. This study discovered and validated the anti-inflammatory effect of Ghrelin in patients with endometriosis. Thus, the data presented open a potential use of Ghrelin as therapy for chronic inflammation-related disorders as endometriosis.

摘要

背景

胃饥饿素是一种由28个氨基酸组成的肽,因其在调节食欲和能量平衡中的作用而被人们所认识。最近,它还被确定为一种免疫调节剂,可显著影响慢性炎症状态下的免疫反应。本文介绍了胃饥饿素对人子宫内膜基质(hEM15A)细胞活力和细胞因子表达的作用,重点关注该肽调节炎症的方式。

方法

在本研究中,培养hEM15A细胞并用浓度范围为1μM至1000μM的胃饥饿素进行处理。使用细胞计数试剂盒-8(CCK-8)测定法评估细胞活力。通过酶联免疫吸附测定(ELISA)测量细胞因子TNF-α、IL-6和IL-10的水平,并通过蛋白质免疫印迹(WB)分析确认胃饥饿素受体的表达。

结果

结果表明胃饥饿素受体(GHSR)在hEM15A细胞中成功表达。细胞活力分析表明,胃饥饿素对细胞增殖有积极影响,尤其是在较高浓度时。ELISA结果显示,促炎细胞因子TNF-α和IL-6显著降低,同时抗炎细胞因子IL-10显著增加,且呈剂量依赖性。

结论

胃饥饿素可通过其受体GHSR发挥作用。同时,胃饥饿素刺激细胞生长而不导致活力下降;它通过平衡一些关键促炎细胞因子的释放,在分子水平上调节炎症,从而具有细胞保护作用。本研究发现并验证了胃饥饿素在子宫内膜异位症患者中的抗炎作用。因此,所呈现的数据为胃饥饿素作为子宫内膜异位症等慢性炎症相关疾病的治疗方法开辟了潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/455309c81dfd/fendo-16-1587490-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/ffbadc9f4ee2/fendo-16-1587490-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/060d1b102cbf/fendo-16-1587490-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/9a73dfe4b22e/fendo-16-1587490-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/455309c81dfd/fendo-16-1587490-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/ffbadc9f4ee2/fendo-16-1587490-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/060d1b102cbf/fendo-16-1587490-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/9a73dfe4b22e/fendo-16-1587490-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfa/12433839/455309c81dfd/fendo-16-1587490-g004.jpg

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