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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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Autores principales: Sharma, Amit, Khan, Md. Abdul Hye, Levick, Scott P., Lee, Kin Sing Stephen, Hammock, Bruce D., Imig, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881572/
https://www.ncbi.nlm.nih.gov/pubmed/27213332
http://dx.doi.org/10.3390/ijms17050751
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author Sharma, Amit
Khan, Md. Abdul Hye
Levick, Scott P.
Lee, Kin Sing Stephen
Hammock, Bruce D.
Imig, John D.
author_facet Sharma, Amit
Khan, Md. Abdul Hye
Levick, Scott P.
Lee, Kin Sing Stephen
Hammock, Bruce D.
Imig, John D.
author_sort Sharma, Amit
collection PubMed
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.
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spelling pubmed-48815722016-05-27 Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis Sharma, Amit Khan, Md. Abdul Hye Levick, Scott P. Lee, Kin Sing Stephen Hammock, Bruce D. Imig, John D. Int J Mol Sci Article 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. MDPI 2016-05-18 /pmc/articles/PMC4881572/ /pubmed/27213332 http://dx.doi.org/10.3390/ijms17050751 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sharma, Amit
Khan, Md. Abdul Hye
Levick, Scott P.
Lee, Kin Sing Stephen
Hammock, Bruce D.
Imig, John D.
Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis
title 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_short Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis
title_sort novel omega-3 fatty acid epoxygenase metabolite reduces kidney fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881572/
https://www.ncbi.nlm.nih.gov/pubmed/27213332
http://dx.doi.org/10.3390/ijms17050751
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