IR@PKUHSC  > 北京大学第一临床医学院  > 泌尿外科
学科主题临床医学
Transforming Growth Factor beta 1 Mediates Apoptotic Activity of Angiotensin II Type I Receptor Blocker on Prostate Epithelium In Vitro
Zhao, Yayuan; Peng, Jing; Zheng, Lanbin; Yu, Wei; Jin, Jie
关键词benign prostatic hyperplasia angiotensin II type I receptor apoptosis transforming growth factor
刊名PROSTATE
2010-06-01
DOI10.1002/pros.21124
70期:8页:899-905
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism ; Urology & Nephrology
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]Endocrinology & Metabolism ; Urology & Nephrology
关键词[WOS]CELL-PROLIFERATION ; CONVERTING ENZYME ; AT1 RECEPTOR ; HYPERPLASIA ; BENIGN ; EXPRESSION ; TISSUE ; RAT ; HYPERTENSION ; HYPERTROPHY
英文摘要

BACKGROUND. The significant association of benign prostatic hyperplasia (BPH) and hypertension indicates a common pathophysiological factor for both diseases. Hyperactivity of the renin-angiotensin system (RAS) has been reported in BPH. Angiotensin IT type I (AT1) receptor is the principal mediator of the RAS, and the antagonist, AT1 receptor blocker (ARB), can induce apoptosis in prostate epithelium cells and increase transforming growth factor beta 1 (TCF-beta 1) expression. We aimed to investigate the mechanism of inhibition of AT1 receptor in prostate epithelium cells and the role of TGF-beta 1.

METHODS. Human prostate epithelium cell lines were treated with different concentrations of ARB (losartan) (0, 0.1, 1, 10, 100, and 1,000 mu M) for 24-72 hr. Cell proliferation was analyzed by cell proliferation assay. The location of AT1 receptor was shown by immunocytohistochemistry and immunocytofluorescence study. Analysis of apoptosis was by use of terminal transferase TdT-mediated dUTP-biotin end labeling (TUNEL) and caspase 3/7 activity assay. Mitochondrial outer-membrane permeabilization was measured by JC-1 staining. The level of TGF-beta 1 was determined by enzyme-linked immunosorbent assay.

RESULTS. Immunohistochemistry and immunofluorescence analysis showed AT1 receptor expressed in epithelium cells. Compared to control cultures, cultures treated with losartan for 24-72 hr showed a dose-dependent significant decrease in cell number, with apoptosis increased by 65.2%. Decreased cell number was reversed on treatment with anti-TGF-beta 1 antibody. TUNEL staining showed increased apoptosis in prostate epithelium cells exposed to losartan. Caspase 3/7 activation was increased and mitochondrial membrane potential was downregulated. Expression of TGF-beta 1 in cells treated with losartan was higher than that in untreated cells.

CONCLUSIONS. The apoptotic effect of blockade of All receptor on human prostatic epithelium cells may be mediated through an autocrine the production of TGF-beta 1. Furthermore, this finding may have implications for medication options. Prostate 70: 899-905, 2010. (C) 2010 Wiley-Liss, Inc.

语种英语
所属项目编号30571851
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000278240600011
Citation statistics
Cited Times:2[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/400002259/67285
Collection北京大学第一临床医学院_泌尿外科
作者单位Peking Univ First Hosp, Dept Urol, Beijing 100034, Peoples R China
Recommended Citation
GB/T 7714
Zhao, Yayuan,Peng, Jing,Zheng, Lanbin,et al. Transforming Growth Factor beta 1 Mediates Apoptotic Activity of Angiotensin II Type I Receptor Blocker on Prostate Epithelium In Vitro[J]. PROSTATE,2010,70(8):899-905.
APA Zhao, Yayuan,Peng, Jing,Zheng, Lanbin,Yu, Wei,&Jin, Jie.(2010).Transforming Growth Factor beta 1 Mediates Apoptotic Activity of Angiotensin II Type I Receptor Blocker on Prostate Epithelium In Vitro.PROSTATE,70(8),899-905.
MLA Zhao, Yayuan,et al."Transforming Growth Factor beta 1 Mediates Apoptotic Activity of Angiotensin II Type I Receptor Blocker on Prostate Epithelium In Vitro".PROSTATE 70.8(2010):899-905.
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