Role of Versican in the Pathogenesis of Peritoneal Endometriosis

Role of Versican in the Pathogenesis of Peritoneal Endometriosis
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DOI:
10.1210/jc.2016-2391
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发表时间:
2016-11-01
影响因子:
5.8
通讯作者:
Shinomura, Tamayuki
Shinomura, Tamayuki
中科院分区:
医学2区
文献类型:
--
作者:
Tani, Hirohiko;Sato, Yukiyasu;Shinomura, Tamayuki

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背景:桑普森的理论不能解释为什么只有一些骑自行车的妇女发展腹膜子宫内膜异位症。很少有研究集中在盆腔腹膜,其中接受子宫内膜组织。我们假设腹膜中的分子改变参与腹膜子宫内膜异位症的发展,并进行了微阵列分析,以比较从患有腹膜子宫内膜异位症(异位性腹膜)和没有(非异位性腹膜)的妇女中取样的宏观正常腹膜。Versican是细胞外基质的主要蛋白多糖成分,是异位腹膜中表达上调的分子之一。目的:探讨Versican在腹膜子宫内膜异位症中的作用。设计、患者和主要结果测量:对子宫内膜异位症和非子宫内膜异位症的腹膜进行RT-PCR、免疫染色和蛋白质印迹。将多功能蛋白聚糖V1亚型稳定转染入中国仓鼠卵巢细胞(CHO-V1)中,采用粘附、侵袭和增殖实验研究CHOV 1衍生的条件培养基(V1-CM)对原代人子宫内膜间质细胞的影响。收集的腹膜液的影响,从卵巢囊肿妇女(卵巢囊肿PF)或细胞因子/生长因子,这被证明是升高卵巢囊肿PF,对versican在人腹膜细胞系(HMrSV 5)的表达也examined.Results:Versican V1的表达水平显着高于卵巢囊肿腹膜。在体外,V1-CM促进附着到HMrSV 5细胞单层以及子宫内膜间质细胞的Matrigel侵袭。虽然多功能蛋白聚糖V1的表达上调TGF-β 1在HMrSV 5细胞,它保持不变,在子宫内膜异位症PF。结论:我们的研究结果表明,腹膜多功能蛋白聚糖参与腹膜子宫内膜异位症的发展。
Context: Sampson's theory cannot explain why only some cycling women develop peritoneal endometriosis. Few studies have focused on the pelvic peritoneum, which receives regurgitated endometrial tissues. We hypothesized that molecular alterations in the peritoneum are involved in the development of peritoneal endometriosis and conducted a microarray analysis to compare macroscopically normal peritoneum sampled from women with peritoneal endometriosis (endometriotic peritoneum) and those without (non-endometriotic peritoneum). Versican, a major proteoglycan component of the extracellular matrix, is one of the molecules up-regulated in endometriotic peritoneum.Objective: To investigate the role of versican in peritoneal endometriosis. Design, Patients, andMain Outcome Measure: Endometriotic peritoneum and non-endometriotic peritoneum were subjected to RT-PCR, immunostaining, and Western blotting. The versican V1 isoform was stably transfected into Chinese hamster ovary cells (CHO-V1), and the effects of CHOV1-derived conditioned medium (V1-CM) on primary human endometrial stromal cells were investigated with attachment, invasion, and proliferation assays. The effects of peritoneal fluid collected from endometriotic women (endometriotic PF) or cytokines/growth factors, which were shown to be elevated in endometriotic PF, on versican expression in a human peritoneal cell line (HMrSV5) were also examined.Results: Versican V1 expression levels were significantly higher in endometriotic peritoneum. In vitro, V1-CM promoted attachment to the HMrSV5 cell monolayer as well as the Matrigel invasion of endometrial stromal cells. Although versican V1 expression was up-regulated by TGF-beta 1 in HMrSV5 cells, it remained unchanged in endometriotic PF.Conclusions: Our results suggest the involvement of peritoneal versican in the development of peritoneal endometriosis.