دورية أكاديمية
Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1)
| العنوان: | Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1) |
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| المؤلفون: | Lin, Wei, Rahman, Nafis A., Lin, Jian, Zhang, Hua, Gou, Kemian, Yu, Wanpeng, Zhu, Dahai, Li, Ning, Huhtaniemi, Ilpo, Li, Xiangdong |
| المساهمون: | Li, XD (reprint author), China Agr Univ, Fac Biol Sci, State Key Lab Agrobiotechnol, Yuanmingyuan W Rd 2, Beijing 100193, Peoples R China., China Agr Univ, Fac Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China., Univ Turku, Dept Physiol, Turku, Finland., Florida Int Univ, Coll Med, Dept Cell Biol, Miami, FL 33199 USA., Florida Int Univ, Coll Med, Dept Mol & Human Genet, Miami, FL 33199 USA., Florida Int Univ, Coll Med, Dept Obstet & Gynecol, Miami, FL 33199 USA., Peking Univ, Inst Urol, Beijing 100871, Peoples R China., Peking Univ, Hosp 1, Dept Urol, Beijing 100871, Peoples R China., Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China., Peking Union Med Coll, Beijing 100021, Peoples R China., Univ London Imperial Coll Sci Technol & Med, Dept Reprod Biol, London, England., China Agr Univ, Fac Biol Sci, State Key Lab Agrobiotechnol, Yuanmingyuan W Rd 2, Beijing 100193, Peoples R China. |
| المصدر: | SCI |
| بيانات النشر: | american journal of pathology |
| سنة النشر: | 2011 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | URINARY-TRACT SYMPTOMS, BENIGN PROSTATIC HYPERPLASIA, ESTROGEN-RECEPTOR-ALPHA, POPULATION-BASED SURVEY, P450 AROMATASE, OVERACTIVE BLADDER, VOIDING SYMPTOMS, ELDERLY-MEN, CANCER, PREVALENCE |
| الوصف: | 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) ; Pathology ; SCI(E) ; 7 ; ARTICLE ; 3 ; 1233-1244 ; 178 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 0002-9440 |
| العلاقة: | AMERICAN JOURNAL OF PATHOLOGY.2011,178,(3),1233-1244.; 912418; http://hdl.handle.net/20.500.11897/240832Test; WOS:000288185600030 |
| DOI: | 10.1016/j.ajpath.2010.11.056 |
| الإتاحة: | https://doi.org/20.500.11897/240832Test https://doi.org/10.1016/j.ajpath.2010.11.056Test https://hdl.handle.net/20.500.11897/240832Test |
| رقم الانضمام: | edsbas.4986661 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00029440 |
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| DOI: | 10.1016/j.ajpath.2010.11.056 |