Document Detail


20-HETE mediates proliferation of renal epithelial cells in polycystic kidney disease.
MedLine Citation:
PMID:  18596124     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polycystic kidney diseases are characterized by abnormal proliferation of renal epithelial cells. In this study, the role of 20-hydroxyeicosatetraenoic acid (20-HETE), an endogenous cytochrome P450 metabolite of arachidonic acid with mitogenic properties, was evaluated in cystic renal disease. Daily administration of HET-0016, an inhibitor of 20-HETE synthesis, significantly reduced kidney size by half in the BPK mouse model of autosomal recessive polycystic kidney disease. In addition, compared with untreated BPK mice, this treatment significantly reduced collecting tubule cystic indices and approximately doubled survival. For evaluation of the role of 20-HETE as a mediator of epithelial cell proliferation, principal cells isolated from cystic BPK and noncystic Balb/c mice were genetically modified using lentiviral vectors. Noncystic Balb/c cells overproducing Cyp4a12 exhibited a four- to five-fold increase in cell proliferation compared with control Balb/c cells, and this increase was completely abolished when 20-HETE synthesis was inhibited; therefore, this study suggests that 20-HETE mediates proliferation of epithelial cells in the formation of renal cysts.
Authors:
Frank Park; William E Sweeney; Guangfu Jia; Richard J Roman; Ellis D Avner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-07-02
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  19     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-29     Completed Date:  2008-10-21     Revised Date:  2013-08-22    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1929-39     Citation Subset:  IM    
Affiliation:
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. fpark@mcw.edu
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MeSH Terms
Descriptor/Qualifier:
Amidines / pharmacology
Animals
Cell Culture Techniques
Cell Proliferation* / drug effects
Cytochrome P-450 Enzyme System / metabolism,  physiology
Disease Models, Animal
Epithelial Cells / physiology*
Hydroxyeicosatetraenoic Acids / antagonists & inhibitors,  physiology*
Mice
Mice, Inbred BALB C
Polycystic Kidney Diseases / etiology*,  metabolism,  pathology*
Grant Support
ID/Acronym/Agency:
HL 36279/HL/NHLBI NIH HHS; P50 DK057306/DK/NIDDK NIH HHS; P50 DK079306/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Amidines; 0/Hydroxyeicosatetraenoic Acids; 0/N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.15.3/Cyp4a12 protein, mouse
Comments/Corrections

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