子宫内膜间充质干细胞在子宫内膜异位症中的内质网应激反应

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-08-28 DOI:10.1016/j.tice.2024.102544
Selenay Furat Rencber , Yusufhan Yazır , Mehmet Sarıhan , Zehra Sezer , Zeynep Ece Utkan Korun , Ahmet Ozturk , Gokhan Duruksu , Elif Guzel , Gurler Akpınar , Aydın Corakci
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引用次数: 0

摘要

目的人体子宫内膜的干细胞具有显著的再生能力,在免疫调节、免疫耐受、类固醇激素反应和炎症方面发挥着重要作用。子宫内膜异位症是一种炎症性妇科疾病,子宫内膜样组织在子宫腔外生长,影响着数百万妇女,并经常导致不孕。最新研究表明,干细胞是子宫内膜异位症的病理因素之一。ER应激与包括子宫内膜异位症在内的多种疾病有关。本研究旨在检测子宫内膜异位症发病机制中eMSCs的ER压力,并揭示潜在的疾病机理。利用蛋白质组分析评估ER应激蛋白水平,并通过Western Blot和免疫荧光染色进行验证。通过 RT-qPCR 分析基因表达,并使用 TEM 对 eMSCs 进行超微结构检查。通过免疫荧光染色检测组织样本中的ER应激标记物,并使用共聚焦显微镜观察SUSD2+ eMSCs。结果 蛋白组学分析发现ER应激相关蛋白(DDRGK1、RTN3、ERp44、TMED2、TMEM33、TMX3)的水平与对照组有显著差异。蛋白水平的 Western 印迹分析和免疫荧光染色结果以及基因水平的 RT-qPCR 结果都支持这些发现。TEM 分析也显示,子宫内膜异位症组的超微结构中存在 ER 应激。我们的研究有望揭示子宫内膜异位症的病理,并为无创诊断和潜在治疗提供有前景的途径。
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Endoplasmic reticulum stress of endometrial mesenchymal stem cells in endometriosis

Objective

The human endometrium has significant regenerative abilities due to stem cells, which are vital in immunomodulation, immune tolerance, steroid hormone response, and inflammation. Endometriosis, an inflammatory gynecological disorder where endometrium-like tissue grows outside uterus, affects millions of women and often causes infertility. Recent research indicates that stem cells contribute to pathology of endometriosis. ER stress is implicated in various diseases, including endometriosis. This study aims to examine ER stress in eMSCs within endometriosis pathogenesis and uncover underlying disease mechanisms.

Methods

Samples were collected from healthy subjects and women with endometriosis in both proliferative and secretory phases. eMSCs were isolated and characterized via flow cytometry. ER stress protein levels were assessed using proteomic analysis, with validation through Western Blot and immunofluorescence staining. Gene expression was analyzed by RT-qPCR, and ultrastructural examination of eMSCs was conducted using TEM. ER stress markers in tissue samples were detected in SUSD2+ eMSCs through immunofluorescence staining and visualized using a confocal microscope. Statistical analysis was performed using SPSS program.

Results

The proteomics analysis uncovered ER stress-related proteins (DDRGK1, RTN3, ERp44, TMED2, TMEM33, TMX3) whose levels were significantly distinct from control group. Western Blot analysis and immunofluorescence staining results at protein level; RT-qPCR results at gene level supported these findings. TEM analysis also showed ultrastructural presence of ER stress in endometriosis groups.

Conclusion

Presence of ER stress in eMSCs in pathogenesis of endometriosis has been demonstrated using various methods. Our research has potential to shed light on pathology of endometriosis and offer promising avenues for non-invasive diagnosis and potential treatment.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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