Results
| PMID | 24423359 |
| Gene Name | NR2F2 |
| Condition | Endometriosis |
| Association |
Associated |
| Population size | 57 |
| Population details | 57 (21 endometrial and 36 endometriotic tissue) |
| Sex | Female |
| Associated genes | COX-2, COUP-TFII |
| Other associated phenotypes |
Endomertiosis |
|
J Clin Endocrinol Metab. 2014 Mar;99(3):E427-37. doi: 10.1210/jc.2013-3717. Epub Lin, Shih-Chieh| Li, Yo-Hua| Wu, Meng-Hsing| Chang, Yu-Fan| Lee, Dong-Kee| Tsai, Sophia Y| Tsai, Ming-Jer| Tsai, Shaw-Jenq Department of Physiology (S.-C.L., Y.-F.C., S.-J.T.), Institute of Basic Medical Sciences (Y.-H.L., S.-J.T.), and Department of Obstetrics and Gynecology (M.-H.W.), College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; and Departm CONTEXT: Endometriosis is one of the most common gynecological diseases in women with a prevalence rate of approximately 10%. Chronic pelvic inflammation has been observed in patients with endometriosis and is associated with disease severity. However, how pelvic inflammation promotes endometriosis progression remains unknown. OBJECTIVE: The objective of the study was to investigate the regulatory network of proinflammatory cytokines in endometriosis progression. DESIGN, SETTINGS, AND PATIENTS: Immunostaining of human endometrial (n = 21) and endometriotic (n = 36) sections, quantitative RT-PCR, Western blotting, chromatin immunoprecipitation, and luciferase reporter assays in primary culture human endometrial stromal cells were performed. Autologous transplantation of uterine endometrium from control chicken ovalbumin upstream promoter-transcription factor II [(COUP-TFII) flox/flox] and uterus-specific COUP-TFII knockout mice was performed. RESULTS: Expression of COUP-TFII was significantly reduced in endometriotic stroma. Reduction of COUP-TFII in endometriotic stromal cells was mediated by proinflammatory cytokines including IL-1beta, TNF-alpha, and TGF-beta1 via a common effector, microRNA-302a. Treatment with these proinflammatory cytokines increased the expression of microRNA-302a, which targets the 3'untranslated region of COUP-TFII to cause its down-regulation. Intriguingly, down-regulation of COUP-TFII in endometrial stromal cells resulted in de-repression of cyclooxygenase-2 (COX-2). Further investigation demonstrated that COUP-TFII directly binds to COX-2 promoter to inhibit its transcription. Forced expression of COUP-TFII inhibited IL-1beta-induced COX-2 up-regulation, whereas the knockdown of COUP-TFII augmented this effect. CONCLUSION: Because overexpression of COX-2 has been demonstrated to be a master regulator in endometriosis progression, our data demonstrate the critical function of proinflammatory cytokines and the COUP-TFII regulatory gene network in the progression of endometriosis. Mesh Terms: Animals| COUP Transcription Factor II/*genetics/metabolism| Cells, Cultured| Cytokines/pharmacology/*physiology| Down-Regulation/drug effects/genetics| Endometriosis/*genetics/metabolism| Endometrium/metabolism/pathology| Female| Gene Regulatory N |
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