摘要
背景:自噬广泛存在于各种生理和病理条件下。大量的研究证实,自噬活性与癌症的发生和发展有关。子宫内膜异位症(EMs)是指子宫内膜样组织在子宫外异常生长的一种疾病,由于其恶性的生物学行为,也被认为具有肿瘤的特征。最近,一些研究已经表明,自噬可能在增殖期胚胎干细胞中发挥潜在作用。然而,自噬活性在分泌期EMs中的作用尚不清楚。方法:探讨正常子宫内膜与子宫内膜病变在不同月经期和不同时期子宫内膜的自噬活性。本研究选取73例女性临床子宫内膜标本,其中30例为正常人,43例为子宫内膜异位症患者(子宫内膜包括在位内膜及其匹配的异位子宫内膜)。按月经周期分为增生期组和分泌期组。在EMs患者中,22例处于增殖期,21例处于分泌期,根据修订后的美国生育学会(R-AFS)将其进一步分为Ⅰ-Ⅱ期和III-Ⅳ期。本研究选择了两种自噬相关蛋白微管相关蛋白1轻链3β-Ⅱ(LC3B-Ⅱ)和螯合小体蛋白(P62)作为自噬活性的指标。采用免疫组织化学(IHC)、Westernblot法和实时定量聚合酶链反应(RTqPCR)检测LC3B-Ⅱ和p62在蛋白和mRNA水平的表达。结果:正常组分泌期LC3B-Ⅱ蛋白和mRNA表达均下降(P<0.0 5),p62表达增加(P<0.0 5),增殖期和分泌期异位及在位子宫内膜表达无显着性差异(P>0.0 5)。此外,异位内膜组LC3B-Ⅱ的表达明显低于在位内膜组(P<0.05),p62的表达也显著高于在位内膜组(P<0.05)。同时,在位子宫内膜组LC3B-Ⅱ和p62水平与对照组比较无显着性差异(P>0.05)。分泌期LC3B-Ⅱ表达明显低于Ⅰ-Ⅱ期组(P<0.05),p62表达显著高于Ⅰ-Ⅱ期组(P<0.05)。结论:EMs的周期性丢失和异位子宫内膜自噬活性的降低可能在EMs的发病机制中发挥潜在作用。分泌期异位子宫内膜自噬下调可能与子宫内膜异位症的进展有关。
关键词: 自噬,子宫内膜异位症,LC3B-Ⅱ,p62,增殖和分泌期,IHC。
Current Gene Therapy
Title:An Observation of the Role of Autophagy in Patients with Endometriosis of Different Stages during Secretory Phase and Proliferative Phase
Volume: 18 Issue: 5
关键词: 自噬,子宫内膜异位症,LC3B-Ⅱ,p62,增殖和分泌期,IHC。
摘要: Background: Autophagy exists widely in various physiological and pathological conditions. Lots of investigations have verified that the autophagic activity is always related to the occurrence and the development of cancer. Endometriosis (EMs) is a disease that endometrium-like tissues abnormally grow outside the uterus and also considered to possess the characters of tumor because of its malignant biological behavior.
Introduction: Recently, several studies have already revealed that autophagy may play a potential role in proliferative-phase EMs. However, the function of autophagic activity in secretory-phase EMs is still unclear.
Methods: In our work, we explored autophagic activity between normal endometrium and EMs lesion endometrium during different menstrual phases and EMs stages. The clinical endometrium samples from 73 women were selected in this study, including 30 healthy individuals and 43 patients with EMs (endometrium samples include eutopic and its matched ectopic endometrium). All the participants were divided into two groups according to the menstrual cycle, namely proliferative-phase and secretive- phase group. Among the patients with EMs, 22 individuals in proliferative phase and the other 21 individuals in secretory phase were further classified into the groups of Stage I-II and Stage III-IV according to revised-American Fertility Society (r-AFS). Two autophagy-related proteins microtubuleassociated protein 1 light chain 3 beta-II (LC3B-II) and sequestosome protein (P62), which are believed to be the indicators of autophagy activity, were chosen in the study. Immunohistochemical (IHC) staining, Western blot assay and Real-Time quantitative Polymerase Chain Reaction (RTqPCR) were used to examine the expression of LC3B-II and P62 in protein and mRNA level accordingly.
Result: It showed that the expression of LC3B-II both in protein and mRNA level decreased and that of P62 increased in secretory phase of the healthy group (P<0.05), but showed no significant difference in ectopic and its eutopic endometrium group during proliferative and secretory phase (P>0.05). In addition, the expression of LC3B-II in ectopic endometrium group was significantly lower than that of its eutopic endometrium group (P<0.05), and the expression of P62 was significantly higher accordingly (P<0.05). At the same time, both LC3B-II and P62 levels remained same between eutopic endometrium group and control group (P>0.05). Furthermore, compared to Stage I-II EMs group, the expression of LC3B-II was significantly lower (P<0.05) and P62 was significantly higher (P<0.05) in Stage III-IV EMs during secretory phase.
Conclusion: Taken together, the periodicity-losing in EMs and the decreased autophagic activity in ectopic endometrium may exert a potential role in the pathogenesis of EMs. Down-regulated autophagy of ectopic endometrium in secretory phase may be related to the progression of EMs.
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An Observation of the Role of Autophagy in Patients with Endometriosis of Different Stages during Secretory Phase and Proliferative Phase, Current Gene Therapy 2018; 18 (5) . https://dx.doi.org/10.2174/1566523218666181008155039
DOI https://dx.doi.org/10.2174/1566523218666181008155039 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
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