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
Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1)
Lin, Wei1; Rahman, Nafis A.2,3,4,5; Lin, Jian6,7; Zhang, Hua1; Gou, Kemian1; Yu, Wanpeng1; Zhu, Dahai8,9; Li, Ning1; Huhtaniemi, Ilpo2,3,10; Li, Xiangdong1
刊名AMERICAN JOURNAL OF PATHOLOGY
2011-03-01
DOI10.1016/j.ajpath.2010.11.056
178期:3页:1233-1244
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pathology
研究领域[WOS]Pathology
关键词[WOS]URINARY-TRACT SYMPTOMS ; BENIGN PROSTATIC HYPERPLASIA ; ESTROGEN-RECEPTOR-ALPHA ; POPULATION-BASED SURVEY ; P450 AROMATASE ; OVERACTIVE BLADDER ; VOIDING SYMPTOMS ; ELDERLY-MEN ; CANCER ; PREVALENCE
英文摘要

We investigated the etiology and molecular mechanisms of bladder outlet obstruction (BOO). Transgenic (Tg) male mice overexpressing aromatase (cyp19a1) under the ubiquitin C promoter in the estrogen-susceptible C57B1/6j genetic background (AROM+/6j) developed inguinal hernia by 2 months and severe BOO by 9 to 10 months, with 100% penetrance. These mice gradually developed uremia, renal failure, renal retention, and finally died. The BOO bladders were threefold larger than in age-matched wild-type (WT) males and were filled with urine on necropsy. Hypotrophic smooth muscle cells formed the thin detrusor urinae muscle, and collagen III accumulation contributed to the reduced compliance of the bladder. p-AKT and ER a expression were up-regulated and Pten expression was down-regulated in the BOO bladder urothelium. Expression of only ER alpha in the intradetrusor fibroblasts suggests a specific role of this estrogen receptor form in urothelial proliferation. Inactivation of Pten, which in turn activated the p-AKT pathway, was strictly related to the activation of the ER a pathway in the BOO bladders. Human relevance for these findings was provided by increased expression of p-AKT, PCNA, and ER alpha and decreased expression of PTEN in severe human BOO samples, compared with subnormal to mild samples. These findings clarify the involvement of estrogen excess and/or imbalance of the androgen/estrogen ratio in the molecular pathogenetic mechanisms of BOO and provide a novel lead into potential treatment strategies for BOO. (Am J Pathol 2011, 178.1233-1244; DOI: 10.1016/j.ajpath.2010.11.056)

语种英语
WOS记录号WOS:000288185600030
项目编号2009CB941701 ; 30671506 ; 7082052 ; 20070019030 ; KYCX09075
资助机构Ministry of Science and Technology (MOST) ; National Natural Science Foundation of China (NSFC) ; Natural Science Foundation of Beijing Council (NSFBC) ; Foundation of the Ministry of Education of China (MOE) ; Scientific Research Foundation of Graduate School of China Agricultural University (SRFGSCAU) ; Academy of Finland ; Finnish Cultural Foundation at Varsinais-Suomi
引用统计
被引频次:17[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/400002259/64314
专题北京大学第一临床医学院_泌尿外科
作者单位1.Univ Turku, Dept Physiol, Turku, Finland
2.Peking Univ, Inst Urol, Beijing 100871, Peoples R China
3.Peking Univ, Hosp 1, Dept Urol, Beijing 100871, Peoples R China
4.China Agr Univ, Fac Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China
5.Florida Int Univ, Coll Med, Dept Cell Biol, Miami, FL 33199 USA
6.Florida Int Univ, Coll Med, Dept Mol & Human Genet, Miami, FL 33199 USA
7.Florida Int Univ, Coll Med, Dept Obstet & Gynecol, Miami, FL 33199 USA
8.Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China
9.Peking Union Med Coll, Beijing 100021, Peoples R China
10.Univ London Imperial Coll Sci Technol & Med, Dept Reprod Biol, London, England
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GB/T 7714
Lin, Wei,Rahman, Nafis A.,Lin, Jian,et al. Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1)[J]. AMERICAN JOURNAL OF PATHOLOGY,2011,178(3):1233-1244.
APA Lin, Wei.,Rahman, Nafis A..,Lin, Jian.,Zhang, Hua.,Gou, Kemian.,...&Li, Xiangdong.(2011).Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1).AMERICAN JOURNAL OF PATHOLOGY,178(3),1233-1244.
MLA Lin, Wei,et al."Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1)".AMERICAN JOURNAL OF PATHOLOGY 178.3(2011):1233-1244.
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