The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis
The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis
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DOI：
10.1016/j.fertnstert.2012.04.047
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发表时间：
2012-08-01
影响因子：
6.7
通讯作者：
Toyokuni, Shinya
中科院分区：
文献类型：
--
作者：
Kobayashi, Hiroharu;Yamashita, Yoriko;Toyokuni, Shinya
目的：了解异位子宫内膜基质细胞在卵巢子宫内膜异位症 (OEM) 中的作用以及不孕和癌变的相关风险。设计：使用来自 OEM 的永生化在位/异位子宫内膜 (-耳) 基质细胞分析分泌蛋白和基因表达。环境：大学。患者：有或没有 OEM 的女性。干预措施：女性子宫内膜 (-耳) 组织样本有或没有 OEM。主要结果指标：对 OEM 中的氧化应激进行免疫组织化学分析、基因表达谱，并通过质谱法鉴定永生化子宫内膜（耳）基质细胞中的分泌蛋白。结果：4-羟基-2-壬烯醛修饰蛋白和羧甲基赖氨酸在 OEM 患者的基质中而不是上皮细胞中丰富，表明存在氧化应激。永生化异位子宫内膜异位基质细胞表现出高 IRP1/IRP2/HIF-1 β 表达，并且比在位同类细胞含有更少的铁和铜含量。表达谱与蛋白质鉴定相结合，揭示补体成分 3 (C3) 和 pentraxin-3 (PTX3) 是永生化异位子宫内膜异位基质细胞分泌的主要蛋白质。补体-3/PTX3促进THP1巨噬细胞分泌多种细胞因子，从而支持M1分化。结论：OEM中的永生化异位子宫内膜异位基质细胞主要分泌C3和PTX3，并表现出铁代谢的差异调节。 （Fertil Steril (R) 2012；98:415-22。(C) 2012，美国生殖医学会。）
Objective: To understand the role of ectopic endometriotic stromal cells in ovarian endometriosis (OEM) and the associated risks for infertility and carcinogenesis.Design: Analyses of secreted proteins and gene expression using immortalized eutopic/ectopic endometrial(-otic) stromal cells from OEM.Setting: University.Patient(s): Women with and without OEM.Intervention(s): Samples of endometrial(-otic) tissue from women with or without OEM.Main Outcome Measure(s): Immunohistochemical analysis of oxidative stress in OEM, gene expression profiles, and the identification of secreted proteins by mass spectrometry in immortalized endometrial(-otic) stromal cells.Result(s): 4-Hydroxy-2-nonenal-modified proteins and carboxymethyllysine were abundant in the stroma, rather than epithelia, of OEM patients, indicating the presence of oxidative stress. Immortalized ectopic endometriotic stromal cells exhibited high IRP1/IRP2/HIF-1 beta expression and contained lower amounts of iron and copper than their eutopic counterparts. Expression profiles, in combination with protein identification, revealed that complement component 3 (C3) and pentraxin-3 (PTX3) are the major proteins secreted from immortalized ectopic endometriotic stromal cells. Complement-3/PTX3 promoted the secretion of various cytokines by THP1 macrophage cells and thus supported M1 differentiation.Conclusion(s): Immortalized ectopic endometriotic stromal cells in OEM predominantly secrete C3 and PTX3 and exhibit a differential regulation of iron metabolism. (Fertil Steril (R) 2012;98:415-22. (C) 2012 by American Society for Reproductive Medicine.)