20-HETE mediates proliferation of renal epithelial cells in polycystic kidney disease. J Am Soc Nephrol 2008 Oct;19(10):1929-39
Date
07/04/2008Pubmed ID
18596124Pubmed Central ID
PMC2551562DOI
10.1681/ASN.2007070771Scopus ID
2-s2.0-54049136052 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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.
Author List
Park F, Sweeney WE, Jia G, Roman RJ, Avner EDAuthor
Ellis D. Avner MD Emeritus Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AmidinesAnimals
Cell Culture Techniques
Cell Proliferation
Cytochrome P-450 Enzyme System
Cytochrome P450 Family 4
Disease Models, Animal
Epithelial Cells
Hydroxyeicosatetraenoic Acids
Mice
Mice, Inbred BALB C
Polycystic Kidney Diseases
