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过氧化物酶体增殖物激活受体γ激动剂抑制子宫内膜异位症在位子宫内膜间质细胞中人端粒酶逆转录酶的表达及芳香化酶活性。

Peroxisome proliferator-activated receptor γ agonist suppresses human telomerase reverse transcriptase expression and aromatase activity in eutopic endometrial stromal cells from endometriosis.

作者信息

Chang Hye Jin, Lee Jae Hoon, Hwang Kyung Joo, Kim Mi Ran, Yoo Jung Hyun

机构信息

Health Promotion Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

出版信息

Clin Exp Reprod Med. 2013 Jun;40(2):67-75. doi: 10.5653/cerm.2013.40.2.67. Epub 2013 Jun 30.

DOI:10.5653/cerm.2013.40.2.67
PMID:23875162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3714431/
Abstract

OBJECTIVE

To investigate the effect of peroxisome proliferator activated receptor γ (PPARγ) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis.

METHODS

Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPARγ agonist).

RESULTS

We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPARγ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin E2 production in the ESCs of endometriosis.

CONCLUSION

This study suggests that PPARγ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

摘要

目的

探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂对子宫内膜异位症患者培养的子宫内膜间质细胞(ESC)增殖特性以及人端粒酶逆转录酶(hTERT)和芳香化酶表达的影响。

方法

采用子宫内膜活检从患有子宫内膜异位症的女性和健康女性(对照组)获取人子宫内膜组织。分离培养ESC,根据罗格列酮(PPARγ激动剂)的添加情况,通过3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐法检测细胞增殖,通过蛋白质印迹法检测hTERT、芳香化酶和环氧化酶(COX)-2的表达。

结果

我们证明,子宫内膜异位症患者培养的ESC显示hTERT蛋白过表达且细胞增殖增加,而罗格列酮以剂量依赖性方式抑制了这种情况。同时,PPARγ激动剂还抑制了芳香化酶和COX-2的表达,导致子宫内膜异位症患者ESC中前列腺素E2的产生减少。

结论

本研究表明,PPARγ激动剂通过下调hTERT和COX-2的表达,对子宫内膜异位症在位子宫内膜的增殖特性发挥抑制作用;这可能是子宫内膜异位症的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/32dcae9bb64e/cerm-40-67-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/98976043f912/cerm-40-67-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/d09bcd7b7a88/cerm-40-67-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/d6f68869f5c8/cerm-40-67-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/32dcae9bb64e/cerm-40-67-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/98976043f912/cerm-40-67-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/d09bcd7b7a88/cerm-40-67-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/d6f68869f5c8/cerm-40-67-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48cc/3714431/32dcae9bb64e/cerm-40-67-g004.jpg

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Reprod Toxicol. 2008 Oct;26(2):183-4. doi: 10.1016/j.reprotox.2008.08.001. Epub 2008 Aug 13.
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Endometriosis is associated with aberrant endometrial expression of telomerase and increased telomere length.
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Hum Reprod. 2008 Jul;23(7):1511-9. doi: 10.1093/humrep/den172. Epub 2008 May 2.
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