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Up-Regulated Expression of WNT5a Increases Inflammation and Oxidative Stress via PI3K/AKT/NF-kappa B Signaling in the Granulosa Cells of PCOS Patients
Zhao, Yue1,2,3; Zhang, Chunmei1,3; Huang, Ying1,2; Yu, Yang1,3; Li, Rong1,3; Li, Min1,2; Liu, Nana1,3; Liu, Ping1,2; Qiao, Jie1,2,3
刊名JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2015
DOI10.1210/jc.2014-2419
100期:1页:201-211
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]POLYCYSTIC-OVARY-SYNDROME ; LOW-GRADE INFLAMMATION ; NORMAL-WEIGHT WOMEN ; C-REACTIVE PROTEIN ; GENE-EXPRESSION ; KAPPA-B ; INSULIN-RESISTANCE ; OBESITY ; MACROPHAGES ; ACTIVATION
英文摘要

Context: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied by chronic low-grade inflammation, but the molecular mechanism remains unclear.

Objective: We investigated the action of WNT5a in the development of chronic inflammation in PCOS and the related molecular signaling pathways.

Design and Setting: This was a prospective study conducted at the Division of Reproduction Center, Peking University Third Hospital.

Patients: A total of 35 PCOS patients and 87 control women who reported to the clinic for the in vitro procedure and the cause of marital infertility was male azoospermia were included.

Main Outcome Measures: Mural granulosa cells (GCs) of 35 PCOS patients and 37 controls were collected during oocyte retrieval and gene expression was analyzed. The human KGN cells and mural GCs from 50 control subjects (six to eight samples were pooled together for each experiment) were cultured in vitro. The regulation of inflammation and oxidative stress was confirmed by quantitative PCR, flow-cytometric assay, and dual-luciferase reporter assay after inflammatory stimuli or WNT5a overexpression. Relevant signaling pathways were identified using specific inhibitors.

Results: Our data demonstrate significantly elevated WNT5a expression in the mural GCs of PCOS patients compared with the controls. Lipopolysaccharide stimulation increased WNT5a expression in KGN cells and mural GCs, and BAY-117082 and pyrrolidine dithiocarbamic acid [nuclear factor-kappa B (NF-kappa B) inhibitor] treatments suppressed WNT5a mRNA below the control level. WNT5a overexpression also enhanced the expression of inflammation-related genes and increased intracellular reactive oxygen species, whereas both BAY-117082 and LY-294002 (phosphatidylinositol 3-kinase inhibitor) significantly inhibited WNT5a-induced inflammation and oxidative stress.

Conclusions: WNT5a acts as a proinflammatory factor in human ovarian GCs. The up-regulated expression of WNT5a in PCOS increases inflammation and oxidative stress predominantly via the phosphatidylinositol 3-kinase/AKT/NF-kappa B signaling pathway. The proinflammatory cytokines induced might further enhance WNT5a expression via NF-kappa B-dependent regulation, indicating a novel regulatory system for chronic inflammation in PCOS.

语种英语
WOS记录号WOS:000353281300069
项目编号2014CB943203 ; 81300457 ; 81170538 ; 20120001120077 ; 2012BAI32B01
资助机构Ministry of Science and Technology of China (973 Program) Grant ; National Natural Science Foundation of China Grant ; Research Fund for the Doctoral Program of Higher Education of China Grant ; National Key Technology Research and Development Program in the Twelve Five-Year Plan Grant
引用统计
被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56531
专题北京大学第三临床医学院_生殖医学中心
北京大学第二临床医学院_麻醉科
北京大学第三临床医学院_妇产科
作者单位1.Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China
2.Peking Univ, Reprod Med Ctr, Hosp 3, Dept Obstet & Gynecol, Beijing 100191, Peoples R China
3.Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhao, Yue,Zhang, Chunmei,Huang, Ying,et al. Up-Regulated Expression of WNT5a Increases Inflammation and Oxidative Stress via PI3K/AKT/NF-kappa B Signaling in the Granulosa Cells of PCOS Patients[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2015,100(1):201-211.
APA Zhao, Yue.,Zhang, Chunmei.,Huang, Ying.,Yu, Yang.,Li, Rong.,...&Qiao, Jie.(2015).Up-Regulated Expression of WNT5a Increases Inflammation and Oxidative Stress via PI3K/AKT/NF-kappa B Signaling in the Granulosa Cells of PCOS Patients.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,100(1),201-211.
MLA Zhao, Yue,et al."Up-Regulated Expression of WNT5a Increases Inflammation and Oxidative Stress via PI3K/AKT/NF-kappa B Signaling in the Granulosa Cells of PCOS Patients".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 100.1(2015):201-211.
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