Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis. Int J Mol Sci 2016 May 18;17(5)
Date
05/24/2016Pubmed ID
27213332Pubmed Central ID
PMC4881572DOI
10.3390/ijms17050751Scopus ID
2-s2.0-84969143046 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
Cytochrome P450 (CYP) monooxygenases epoxidize the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid into novel epoxydocosapentaenoic acids (EDPs) that have multiple biological actions. The present study determined the ability of the most abundant EDP regioisomer, 19,20-EDP to reduce kidney injury in an experimental unilateral ureteral obstruction (UUO) renal fibrosis mouse model. Mice with UUO developed kidney tubular injury and interstitial fibrosis. UUO mice had elevated kidney hydroxyproline content and five-times greater collagen positive fibrotic area than sham control mice. 19,20-EDP treatment to UUO mice for 10 days reduced renal fibrosis with a 40%-50% reduction in collagen positive area and hydroxyproline content. There was a six-fold increase in kidney α-smooth muscle actin (α-SMA) positive area in UUO mice compared to sham control mice, and 19,20-EDP treatment to UUO mice decreased α-SMA immunopositive area by 60%. UUO mice demonstrated renal epithelial-to-mesenchymal transition (EMT) with reduced expression of the epithelial marker E-cadherin and elevated expression of multiple mesenchymal markers (FSP-1, α-SMA, and desmin). Interestingly, 19,20-EDP treatment reduced renal EMT in UUO by decreasing mesenchymal and increasing epithelial marker expression. Overall, we demonstrate that a novel omega-3 fatty acid metabolite 19,20-EDP, prevents UUO-induced renal fibrosis in mice by reducing renal EMT.
Author List
Sharma A, Hye Khan MA, Levick SP, Lee KS, Hammock BD, Imig JDMESH terms used to index this publication - Major topics in bold
ActinsAnimals
Collagen
Disease Models, Animal
Epithelial-Mesenchymal Transition
Fatty Acids, Omega-3
Fatty Acids, Unsaturated
Gene Expression Regulation
Humans
Hydroxyproline
Kidney Diseases
Male
Mice
Stereoisomerism