Cargando…

Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression

Epidemiologic studies showed the correlation between the deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the progression of chronic kidney diseases (CKD), however, the role and mechanisms for n-3 PUFAs in protecting against kidney fibrosis remain obscure. In this study, NRK-49F cel...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeng, Zhifeng, Yang, Haiyuan, Wang, Ying, Ren, Jiafa, Dai, Yifan, Dai, Chunsun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385873/
https://www.ncbi.nlm.nih.gov/pubmed/28393852
http://dx.doi.org/10.1038/srep46146
_version_ 1782520667116142592
author Zeng, Zhifeng
Yang, Haiyuan
Wang, Ying
Ren, Jiafa
Dai, Yifan
Dai, Chunsun
author_facet Zeng, Zhifeng
Yang, Haiyuan
Wang, Ying
Ren, Jiafa
Dai, Yifan
Dai, Chunsun
author_sort Zeng, Zhifeng
collection PubMed
description Epidemiologic studies showed the correlation between the deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the progression of chronic kidney diseases (CKD), however, the role and mechanisms for n-3 PUFAs in protecting against kidney fibrosis remain obscure. In this study, NRK-49F cells, a rat kidney interstitial fibroblast cell line, were stimulated with TGFβ1. A Caenorhabditis elegans fat-1 transgenic mouse model in which n-3 PUFAs are endogenously produced from n-6 PUFAs owing to the expression of n-3 fatty acid desaturase were deployed. Docosahexaenoic acid (DHA), one member of n-3 PUFAs family, could suppress TGFβ1-induced fibroblast activation at a dose and time dependent manner. Additionally, DHA could largely inhibit TGFβ1-stimulated Akt but not S6 or Smad3 phosphorylation at a time dependent manner. To decipher the role for n-3 PUFAs in protecting against kidney fibrosis, fat-1 transgenic mice were operated with unilateral ureter obstruction (UUO). Compared to the wild types, fat-1 transgenics developed much less kidney fibrosis and inflammatory cell accumulation accompanied by less p-Akt (Ser473), p-Akt (Thr308), p-S6 and p-Smad3 in kidney tissues at day 7 after UUO. Thus, n-3 PUFAs can attenuate fibroblast activation and kidney fibrosis, which may be associated with the inhibition of mTORC2 signaling.
format Online
Article
Text
id pubmed-5385873
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-53858732017-04-12 Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression Zeng, Zhifeng Yang, Haiyuan Wang, Ying Ren, Jiafa Dai, Yifan Dai, Chunsun Sci Rep Article Epidemiologic studies showed the correlation between the deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the progression of chronic kidney diseases (CKD), however, the role and mechanisms for n-3 PUFAs in protecting against kidney fibrosis remain obscure. In this study, NRK-49F cells, a rat kidney interstitial fibroblast cell line, were stimulated with TGFβ1. A Caenorhabditis elegans fat-1 transgenic mouse model in which n-3 PUFAs are endogenously produced from n-6 PUFAs owing to the expression of n-3 fatty acid desaturase were deployed. Docosahexaenoic acid (DHA), one member of n-3 PUFAs family, could suppress TGFβ1-induced fibroblast activation at a dose and time dependent manner. Additionally, DHA could largely inhibit TGFβ1-stimulated Akt but not S6 or Smad3 phosphorylation at a time dependent manner. To decipher the role for n-3 PUFAs in protecting against kidney fibrosis, fat-1 transgenic mice were operated with unilateral ureter obstruction (UUO). Compared to the wild types, fat-1 transgenics developed much less kidney fibrosis and inflammatory cell accumulation accompanied by less p-Akt (Ser473), p-Akt (Thr308), p-S6 and p-Smad3 in kidney tissues at day 7 after UUO. Thus, n-3 PUFAs can attenuate fibroblast activation and kidney fibrosis, which may be associated with the inhibition of mTORC2 signaling. Nature Publishing Group 2017-04-10 /pmc/articles/PMC5385873/ /pubmed/28393852 http://dx.doi.org/10.1038/srep46146 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zeng, Zhifeng
Yang, Haiyuan
Wang, Ying
Ren, Jiafa
Dai, Yifan
Dai, Chunsun
Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression
title Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression
title_full Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression
title_fullStr Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression
title_full_unstemmed Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression
title_short Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression
title_sort omega-3 polyunsaturated fatty acids attenuate fibroblast activation and kidney fibrosis involving mtorc2 signaling suppression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385873/
https://www.ncbi.nlm.nih.gov/pubmed/28393852
http://dx.doi.org/10.1038/srep46146
work_keys_str_mv AT zengzhifeng omega3polyunsaturatedfattyacidsattenuatefibroblastactivationandkidneyfibrosisinvolvingmtorc2signalingsuppression
AT yanghaiyuan omega3polyunsaturatedfattyacidsattenuatefibroblastactivationandkidneyfibrosisinvolvingmtorc2signalingsuppression
AT wangying omega3polyunsaturatedfattyacidsattenuatefibroblastactivationandkidneyfibrosisinvolvingmtorc2signalingsuppression
AT renjiafa omega3polyunsaturatedfattyacidsattenuatefibroblastactivationandkidneyfibrosisinvolvingmtorc2signalingsuppression
AT daiyifan omega3polyunsaturatedfattyacidsattenuatefibroblastactivationandkidneyfibrosisinvolvingmtorc2signalingsuppression
AT daichunsun omega3polyunsaturatedfattyacidsattenuatefibroblastactivationandkidneyfibrosisinvolvingmtorc2signalingsuppression