首页|17β-Estradiol,through activating the G protein-coupled estrogen receptor,exacerbates the complication of benign prostatic hyperplasia in type 2 diabetes mellitus patients by inducing prostate proliferation

17β-Estradiol,through activating the G protein-coupled estrogen receptor,exacerbates the complication of benign prostatic hyperplasia in type 2 diabetes mellitus patients by inducing prostate proliferation

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Sex steroid hormone homeostasisProliferation17β-EstradiolG protein-coupled estrogen receptorT2DM complicated with BPHHippo-YAP1 signaling

Tingting Yang、Zhen Qiu、Jiaming Shen、Yutian He、Longxiang Yin、Li Chen、Jiayu Yuan、Junjie Liu、Tao Wang、Zhenzhou Jiang、Changjiang Ying、Sitong Qian、Jinfang Song、Xiaoxing Yin、Qian Lu

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Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu,221004,China

Department of Urology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,China

Department of Pharmacy,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,China

New Drug Screening Center,Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University,Nanjing 210009,China

Department of Endocrinology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,China

Department of Pharmacy,The Affiliated Hospital of Jiangnan University,Wuxi,Jiangsu,214000,China

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2024

10.1016/j.jpha.2024.03.003

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(9)