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Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation

The unilateral ureteral obstruction (UUO) injury model is well-known to mimic human chronic kidney disease, promoting the rapid onset and development of kidney injury. ω3-poly unsaturated fatty acids (PUFAs) have been observed to protect against tissue injury in many disease models. In this study, w...

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Autores principales: Han, Suyeon, Choi, Hyunsu, Park, Hyerim, Kim, Jwa-Jin, Lee, Eu-Jin, Ham, Young-Rok, Na, Ki-Rayng, Lee, Kang-Wook, Chang, Yoon-Kyung, Choi, Dae-Eun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525956/
https://www.ncbi.nlm.nih.gov/pubmed/37760994
http://dx.doi.org/10.3390/biomedicines11092553
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author Han, Suyeon
Choi, Hyunsu
Park, Hyerim
Kim, Jwa-Jin
Lee, Eu-Jin
Ham, Young-Rok
Na, Ki-Rayng
Lee, Kang-Wook
Chang, Yoon-Kyung
Choi, Dae-Eun
author_facet Han, Suyeon
Choi, Hyunsu
Park, Hyerim
Kim, Jwa-Jin
Lee, Eu-Jin
Ham, Young-Rok
Na, Ki-Rayng
Lee, Kang-Wook
Chang, Yoon-Kyung
Choi, Dae-Eun
author_sort Han, Suyeon
collection PubMed
description The unilateral ureteral obstruction (UUO) injury model is well-known to mimic human chronic kidney disease, promoting the rapid onset and development of kidney injury. ω3-poly unsaturated fatty acids (PUFAs) have been observed to protect against tissue injury in many disease models. In this study, we assessed the efficacy of ω3-PUFAs in attenuating UUO injury and investigated their mechanism of action. The immortalized human proximal tubular cells human kidney-2 (HK2) were incubated for 72 h with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) in various concentrations, in the presence or absence of transforming growth factor (TGF)-β. DHA/EPA reduced the epithelial–mesenchymal transition in the TGF-β-treated HK2 cells by enhancing autophagy flux and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. C57BL/6 mice were divided into four groups and treated as follows: sham (no treatment, n = 5), sham + ω3-PUFAs (n = 5), UUO (n = 10), and UUO + ω3-PUFAs (n = 10). Their kidneys and blood were harvested on the seventh day following UUO injury. The kidneys of the ω3-PUFAs-treated UUO mice showed less oxidative stress, inflammation, and fibrosis compared to those of the untreated UUO mice. Greater autophagic flux, higher amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7, lower amounts of p62, and higher levels of cathepsin D and ATP6E were observed in the kidneys of the omega-3-treated UUO mice compared to those of the control UUO mice. In conclusion, ω3-PUFAs enhanced autophagic activation, leading to a renoprotective response against chronic kidney injury.
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spelling pubmed-105259562023-09-28 Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation Han, Suyeon Choi, Hyunsu Park, Hyerim Kim, Jwa-Jin Lee, Eu-Jin Ham, Young-Rok Na, Ki-Rayng Lee, Kang-Wook Chang, Yoon-Kyung Choi, Dae-Eun Biomedicines Article The unilateral ureteral obstruction (UUO) injury model is well-known to mimic human chronic kidney disease, promoting the rapid onset and development of kidney injury. ω3-poly unsaturated fatty acids (PUFAs) have been observed to protect against tissue injury in many disease models. In this study, we assessed the efficacy of ω3-PUFAs in attenuating UUO injury and investigated their mechanism of action. The immortalized human proximal tubular cells human kidney-2 (HK2) were incubated for 72 h with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) in various concentrations, in the presence or absence of transforming growth factor (TGF)-β. DHA/EPA reduced the epithelial–mesenchymal transition in the TGF-β-treated HK2 cells by enhancing autophagy flux and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. C57BL/6 mice were divided into four groups and treated as follows: sham (no treatment, n = 5), sham + ω3-PUFAs (n = 5), UUO (n = 10), and UUO + ω3-PUFAs (n = 10). Their kidneys and blood were harvested on the seventh day following UUO injury. The kidneys of the ω3-PUFAs-treated UUO mice showed less oxidative stress, inflammation, and fibrosis compared to those of the untreated UUO mice. Greater autophagic flux, higher amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7, lower amounts of p62, and higher levels of cathepsin D and ATP6E were observed in the kidneys of the omega-3-treated UUO mice compared to those of the control UUO mice. In conclusion, ω3-PUFAs enhanced autophagic activation, leading to a renoprotective response against chronic kidney injury. MDPI 2023-09-17 /pmc/articles/PMC10525956/ /pubmed/37760994 http://dx.doi.org/10.3390/biomedicines11092553 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Suyeon
Choi, Hyunsu
Park, Hyerim
Kim, Jwa-Jin
Lee, Eu-Jin
Ham, Young-Rok
Na, Ki-Rayng
Lee, Kang-Wook
Chang, Yoon-Kyung
Choi, Dae-Eun
Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation
title Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation
title_full Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation
title_fullStr Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation
title_full_unstemmed Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation
title_short Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation
title_sort omega-3 fatty acids attenuate renal fibrosis via ampk-mediated autophagy flux activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525956/
https://www.ncbi.nlm.nih.gov/pubmed/37760994
http://dx.doi.org/10.3390/biomedicines11092553
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