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学科主题: 基础医学
题名:
Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models
作者: Zhou, Hong1,2; Gao, Jinsheng1,2,3; Zhou, Li1,2; Li, Xin1,2; Li, Weidong1,2; Li, Xuejun1,2; Xia, Yin4,5; Yang, Baoxue1,2
关键词: natural product ; ADPKD ; MAPK
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
发表日期: 2012-05-01
DOI: 10.1152/ajprenal.00356.2011
卷: 302, 期:10, 页:F1234-F1242
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Physiology ; Urology & Nephrology
研究领域[WOS]: Physiology ; Urology & Nephrology
关键词[WOS]: POLYCYSTIC KIDNEY-DISEASE ; BRANCHING MORPHOGENESIS ; SIGNALING PATHWAYS ; EPITHELIAL-CELLS ; CYCLIC-AMP ; ACTIVATION ; GROWTH ; CYSTOGENESIS ; KINASE ; BILOBA
英文摘要:

Zhou H, Gao J, Zhou L, Li X, Li W, Li X, Xia Y, Yang B. Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models. Am J Physiol Renal Physiol 302: F1234-F1242, 2012. First published February 15, 2012; doi:10.1152/ajprenal.00356.2011.-Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by massive enlargement of fluid-filled cysts in the kidney. However, there is no effective therapy yet for this disease. To examine whether ginkgolide B, a natural compound, inhibits cyst development, a Madin-Darby canine kidney (MDCK) cyst model, an embryonic kidney cyst model, and a PKD mouse model were used. Interestingly, ginkgolide B significantly inhibited MDCK cyst formation dose dependently, with up to 69% reduction by 2 mu M ginkgolide B. Ginkgolide B also significantly inhibited cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse model. To determine the underlying mechanisms, the effect of ginkgolide B on MDCK cell viability, proliferation, apoptosis, chloride transporter CFTR activity, and intracellular signaling pathways were also studied. Ginkgolide B did not affect cell viability, proliferation, and expression and activity of the chloride transporter CFTR that mediates cyst fluid secretion. Ginkgolide B induced cyst cell differentiation and altered the Ras/MAPK signaling pathway. Taken together, our results demonstrate that ginkgolide B inhibits renal cyst formation and enlargement, suggesting that ginkgolide B might be developed into a novel candidate drug for ADPKD.

语种: 英语
所属项目编号: 30870921 ; 81170632 ; 2009ZX09301-010-30 ; 20100001110047 ; 2012DFA11070 ; 7102105 ; P30 DK090744
项目资助者: National Natural Science Foundation of China ; Drug Discovery Program Grant ; Research Fund for the Doctoral Program of Higher Education ; Ministry of Science and Technology ; Beijing Natural Science Foundation
WOS记录号: WOS:000304356400002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63938
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100191, Peoples R China
3.Shanxi Prov Hosp Tradit Chinese Med, Dept Oncol, Taiyuan, Peoples R China
4.Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
5.Jinan Univ, Chinese Univ Hong Kong Key Lab Regenerat Med, Minist Educ, Beijing, Peoples R China

Recommended Citation:
Zhou, Hong,Gao, Jinsheng,Zhou, Li,et al. Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,2012,302(10):F1234-F1242.
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