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

• Published in: Biomedicines Vol. 11; no. 9; p. 2553
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2023; MDPI
• Subjects: Adenosine kinase; AMP; Analysis; Antibodies; Autophagy; autophagy flux; Cathepsin D; Chronic kidney failure; Dehydrogenases; Docosahexaenoic acid; Eicosapentaenoic acid; Fatty acids; Fibrosis; Injuries; Kidney diseases; Kinases; Laboratories; Medical research; Medicine, Experimental; Microscopy; Microtubule-associated protein 1; Omega-3 fatty acids; Oxidative stress; Phosphorylation; Polyunsaturated fatty acids; Protein kinases; Proteins; renal fibrosis; Transforming growth factor-b; Transforming growth factors; Unsaturated fatty acids; UUO; ω3-PUFA; United Kingdom; South Korea; St Louis Missouri; United Kingdom > UK; United States > US
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11092553

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.