The beneficial effects of ω3-PUFA on renal fibrosis via AMPK-mediated autophagy flux.

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E-Poster

Abstract Title

First Name *

Dae Eun

Last Name *

Choi

Co-author 1

Ki Ryang Na drngr@hanmail.net Chungnam National University Hospital Nephrology Daejeon

Co-author 2

Suyeon Han sooyaa1208@gmail.com Daejeon Saint Mary Hospital Nephrology Daejeon

Co-author 3

Young Rok Ham youngrok01@cnuh.co.kr Chungnam National University Hospital Nephrology Daejeon

Co-author 4

Eu Jin Lee eujinlee@cnuh.co.kr Chungnam National University Hospital Nephrology Daejeon

Co-author 5

Hyerim Park hye05240@gmail.com Chungnam National University Medical Science Daejeon

Co-author 6

Yoon-Kyung Chang racer@catholic.ac.kr Daejeon Saint Mary Hospital Nephrology Daejeon

Co-author 7

Moo Jun Kim kimmoojun@cnuh.co.kr Chungnam National University Sejong Hospital Nephrology Sejong

Co-author 8

Hae Ri Kim yo0118@cnuh.co.kr Chungnam National University Sejong Hospital Nephrology Sejong

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

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.

Methods

TGF-β-treated-Human kidney-2 (HK-2) cells were used for evaluation of renal fibrosis. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were used for in vitro experiment for ω3-PUFAs. C57BL/6 mice (10 weeks old, male) were used for UUO mice. Molecular analysis via realtime RT PCR and western blot for autophagy targeting gene and protein. Various stains for fibrosis were performed in kidney section.

Results

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.

Conclusions

ω3-PUFAs enhanced autophagic activation, leading to a renoprotective response against chronic kidney injury.

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