Document Detail


Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models.
MedLine Citation:
PMID:  22338085     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 μM 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.
Authors:
Hong Zhou; Jinsheng Gao; Li Zhou; Xin Li; Weidong Li; Xuejun Li; Yin Xia; Baoxue Yang
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-15
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  302     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-16     Completed Date:  2012-07-18     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1234-42     Citation Subset:  IM    
Affiliation:
Dept. of Pharmacology. School of Basic Medical Sciences, Peking Univ., 38 Xueyuan Lu, Haidian District, Beijing 100191, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Cyclic AMP / metabolism
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
Disease Models, Animal
Dogs
Female
Forskolin / pharmacology
Ginkgolides / pharmacology*
Kidney / cytology,  drug effects*,  embryology
Lactones / pharmacology*
MAP Kinase Signaling System / drug effects,  physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Plant Extracts / pharmacology
Polycystic Kidney, Autosomal Dominant / drug therapy*,  genetics,  prevention & control*
Pregnancy
Protein Kinase C / genetics
Chemical
Reg. No./Substance:
0/Ginkgolides; 0/Lactones; 0/Plant Extracts; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 99796-69-7/ginkgolide B; EC 2.7.10.-/protein kinase D; EC 2.7.11.13/Protein Kinase C
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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