Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis

Shih Chieh Lin, Yo Hua Li, Meng Hsing Wu, Yu Fan Chang, Dong Kee Lee, Sophia Y. Tsai, Ming Jer Tsai, Shaw Jenq Tsai

研究成果: Article

17 引文 (Scopus)

摘要

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-1β, TNF-α, and TGF-β1 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-1β-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.

原文English
頁(從 - 到)E427-E437
期刊Journal of Clinical Endocrinology and Metabolism
99
發行號3
DOIs
出版狀態Published - 2014 三月

指紋

COUP Transcription Factor II
Endometriosis
Cytokines
Cyclooxygenase 2
Stromal Cells
MicroRNAs
Interleukin-1
Down-Regulation
Inflammation
Autologous Transplantation
Gene Regulatory Networks
Chromatin Immunoprecipitation
3' Untranslated Regions
Transcription
Endometrium
Luciferases
Knockout Mice

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

引用此文

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title = "Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis",
abstract = "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-1β, TNF-α, and TGF-β1 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-1β-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.",
author = "Lin, {Shih Chieh} and Li, {Yo Hua} and Wu, {Meng Hsing} and Chang, {Yu Fan} and Lee, {Dong Kee} and Tsai, {Sophia Y.} and Tsai, {Ming Jer} and Tsai, {Shaw Jenq}",
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Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis. / Lin, Shih Chieh; Li, Yo Hua; Wu, Meng Hsing; Chang, Yu Fan; Lee, Dong Kee; Tsai, Sophia Y.; Tsai, Ming Jer; Tsai, Shaw Jenq.

於: Journal of Clinical Endocrinology and Metabolism, 卷 99, 編號 3, 03.2014, p. E427-E437.

研究成果: Article

TY - JOUR

T1 - Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis

AU - Lin, Shih Chieh

AU - Li, Yo Hua

AU - Wu, Meng Hsing

AU - Chang, Yu Fan

AU - Lee, Dong Kee

AU - Tsai, Sophia Y.

AU - Tsai, Ming Jer

AU - Tsai, Shaw Jenq

PY - 2014/3

Y1 - 2014/3

N2 - 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-1β, TNF-α, and TGF-β1 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-1β-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.

AB - 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-1β, TNF-α, and TGF-β1 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-1β-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.

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