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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

引用

Journal of Pharmaceutical Analysis 2024年第9期14卷 1372-1386页

作者： 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 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China Department of Endocrinology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy The Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

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 *** 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 *** 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 *** 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 *** 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 *** GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs proliferation through the formation of the YAP1-tEAD4 *** or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated bph-1 *** anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated bph-1 *** E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of t2dm complicated with bph by inhibiting PECs proliferation.

关键词： Sex steroid hormone homeos tasis Proliferation 17β-Estradiol G protein-coupled estrogen receptor t2dm complicated with bph Hippo-YAP1 signaling

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