Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis
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 ki...
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doaj-f8a5560c07ff45628c2e8fae6df76a9f2020-11-25T01:30:36ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-05-0117575110.3390/ijms17050751ijms17050751Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney FibrosisAmit Sharma0Md. Abdul Hye Khan1Scott P. Levick2Kin Sing Stephen Lee3Bruce D. Hammock4John D. Imig5Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USADepartment of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USADepartment of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USADepartment of Entomology & Cancer Center, University of California, Davis, CA 95616, USADepartment of Entomology & Cancer Center, University of California, Davis, CA 95616, USADepartment of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USACytochrome 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.http://www.mdpi.com/1422-0067/17/5/751omega-3 fatty acidfatty acid epoxiderenal fibrosisepithelial-to-mesenchymal transition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amit Sharma Md. Abdul Hye Khan Scott P. Levick Kin Sing Stephen Lee Bruce D. Hammock John D. Imig |
spellingShingle |
Amit Sharma Md. Abdul Hye Khan Scott P. Levick Kin Sing Stephen Lee Bruce D. Hammock John D. Imig Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis International Journal of Molecular Sciences omega-3 fatty acid fatty acid epoxide renal fibrosis epithelial-to-mesenchymal transition |
author_facet |
Amit Sharma Md. Abdul Hye Khan Scott P. Levick Kin Sing Stephen Lee Bruce D. Hammock John D. Imig |
author_sort |
Amit Sharma |
title |
Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis |
title_short |
Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis |
title_full |
Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis |
title_fullStr |
Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis |
title_full_unstemmed |
Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis |
title_sort |
novel omega-3 fatty acid epoxygenase metabolite reduces kidney fibrosis |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2016-05-01 |
description |
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. |
topic |
omega-3 fatty acid fatty acid epoxide renal fibrosis epithelial-to-mesenchymal transition |
url |
http://www.mdpi.com/1422-0067/17/5/751 |
work_keys_str_mv |
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