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学科主题临床医学
Metformin Inhibits StAR Expression in Human Endometriotic Stromal Cells via AMPK-Mediated Disruption of CREB-CRTC2 Complex Formation
Xu, Jia-Ning; Zeng, Cheng; Zhou, Yan; Peng, Chao; Zhou, Ying-Fang; Xue, Qing
刊名JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2014-08-01
DOI10.1210/jc.2014-1593
99期:8页:2795-2803
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]ACUTE REGULATORY PROTEIN ; ELEMENT-BINDING PROTEIN ; STEROIDOGENIC-FACTOR-I ; AROMATASE EXPRESSION ; ACTIVATION ; BREAST ; CREB ; PROLIFERATION ; TRANSCRIPTION ; COACTIVATORS
英文摘要

Context: Endometriosis is an estrogen-dependent disease affecting reproductive women. Metformin could have a therapeutic effect on endometriosis through regulation of local estrogen production.

Objects: The aim of this study was to investigate the molecular and cellular mechanism by which metformin regulates StAR expression in human endometriotic stromal cells (ESCs).

Methods: ESCs derived from ovarian endometriomas were cultured with metformin and prostaglandin E2 (PGE2). StAR mRNA was measured by quantitative PCR; pregnenolone, progesterone, and estrogen production were measured by ELISA kits; steroidogenic acute regulatory protein (StAR), AMP-activated protein kinase, cAMP response element binding protein (CREB), and CREB-regulated transcription coactivator 2 (CRTC2) protein expression were measured by Western blot assay; and CRTC2 translocation and its association with CREB were assessed by coimmunoprecipitation assay and CRTC2-CREB complex binding by a chromatin immunoprecipitation assay.

Results: 1) StAR mRNA levels in ESCs are 264 times higher than those in endometrial cells. 2) Metformin downregulates the StAR mRNA expression (maximum 31.7%) stimulated by PGE2 (2.4-fold) in ESCs. 3) PGE2 induces CRTC2 translocation and enhances its association with CREB to form a transcription complex that binds to the StAR promoter region. 4) Metformin prevents the nuclear translocation of CRTC2 by increasing AMP-activated protein kinase phosphorylation. This inhibits transcription of StAR by disrupting formation of the CREB-CRTC2 complex, involved in activation of the StAR promoter cAMP response element.

Conclusions: We have demonstrated a detailed mechanistic analysis of StAR expression regulated by metformin in ESCs. Our data highlight a role for CRTC2 in the mechanism by which metformin inhibits StAR expression.

语种英语
WOS记录号WOS:000342341200053
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67426
Collection北京大学第一临床医学院
北京大学第一临床医学院_妇产科
北京大学第三临床医学院_放射科
作者单位Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100034, Peoples R China
Recommended Citation
GB/T 7714
Xu, Jia-Ning,Zeng, Cheng,Zhou, Yan,et al. Metformin Inhibits StAR Expression in Human Endometriotic Stromal Cells via AMPK-Mediated Disruption of CREB-CRTC2 Complex Formation[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2014,99(8):2795-2803.
APA Xu, Jia-Ning,Zeng, Cheng,Zhou, Yan,Peng, Chao,Zhou, Ying-Fang,&Xue, Qing.(2014).Metformin Inhibits StAR Expression in Human Endometriotic Stromal Cells via AMPK-Mediated Disruption of CREB-CRTC2 Complex Formation.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,99(8),2795-2803.
MLA Xu, Jia-Ning,et al."Metformin Inhibits StAR Expression in Human Endometriotic Stromal Cells via AMPK-Mediated Disruption of CREB-CRTC2 Complex Formation".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 99.8(2014):2795-2803.
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