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Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis

Following a chronic insult, renal tubular epithelial cells (TECs) contribute to the development of kidney fibrosis through dysregulated lipid metabolism that lead to lipid accumulation and lipotoxicity. Intracellular lipid metabolism is tightly controlled by fatty acids (FAs) uptake, oxidation, lipo...

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Autores principales: Chen, Yuting, Yan, Qi, Lv, Mengyue, Song, Kaixin, Dai, Yue, Huang, Yi, Zhang, Le, Zhang, Cuntai, Gao, Hongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679409/
https://www.ncbi.nlm.nih.gov/pubmed/33219209
http://dx.doi.org/10.1038/s41419-020-03199-x
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author Chen, Yuting
Yan, Qi
Lv, Mengyue
Song, Kaixin
Dai, Yue
Huang, Yi
Zhang, Le
Zhang, Cuntai
Gao, Hongyu
author_facet Chen, Yuting
Yan, Qi
Lv, Mengyue
Song, Kaixin
Dai, Yue
Huang, Yi
Zhang, Le
Zhang, Cuntai
Gao, Hongyu
author_sort Chen, Yuting
collection PubMed
description Following a chronic insult, renal tubular epithelial cells (TECs) contribute to the development of kidney fibrosis through dysregulated lipid metabolism that lead to lipid accumulation and lipotoxicity. Intracellular lipid metabolism is tightly controlled by fatty acids (FAs) uptake, oxidation, lipogenesis, and lipolysis. Although it is widely accepted that impaired fatty acids oxidation (FAO) play a crucial role in renal fibrosis progression, other lipid metabolic pathways, especially FAs uptake, has not been investigated in fibrotic kidney. In this study, we aim to explore the potential mechanically role of FAs transporter in the pathogenesis of renal fibrosis. In the present study, the unbiased gene expression studies showed that fatty acid transporter 2 (FATP2) was one of the predominant expressed FAs transport in TECs and its expression was tightly associated with the decline of renal function. Treatment of unilateral ureteral obstruction (UUO) kidneys and TGF-β induced TECs with FATP2 inhibitor (FATP2i) lipofermata restored the FAO activities and alleviated fibrotic responses both in vivo and in vitro. Moreover, the expression of profibrotic cytokines including TGF-β, connective tissue growth factor (CTGF), fibroblast growth factor (FGF), and platelet-derived growth factor subunit B (PDGFB) were all decreased in FATP2i-treated UUO kidneys. Mechanically, FATP2i can effectively attenuate cell apoptosis and endoplasmic reticulum (ER) stress induced by TGF-β treatment in cultured TECs. Taking together, these findings reveal that FATP2 elicits a profibrotic response to renal interstitial fibrosis by inducing lipid metabolic reprogramming including abnormal FAs uptake and defective FAO in TECs.
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spelling pubmed-76794092020-11-24 Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis Chen, Yuting Yan, Qi Lv, Mengyue Song, Kaixin Dai, Yue Huang, Yi Zhang, Le Zhang, Cuntai Gao, Hongyu Cell Death Dis Article Following a chronic insult, renal tubular epithelial cells (TECs) contribute to the development of kidney fibrosis through dysregulated lipid metabolism that lead to lipid accumulation and lipotoxicity. Intracellular lipid metabolism is tightly controlled by fatty acids (FAs) uptake, oxidation, lipogenesis, and lipolysis. Although it is widely accepted that impaired fatty acids oxidation (FAO) play a crucial role in renal fibrosis progression, other lipid metabolic pathways, especially FAs uptake, has not been investigated in fibrotic kidney. In this study, we aim to explore the potential mechanically role of FAs transporter in the pathogenesis of renal fibrosis. In the present study, the unbiased gene expression studies showed that fatty acid transporter 2 (FATP2) was one of the predominant expressed FAs transport in TECs and its expression was tightly associated with the decline of renal function. Treatment of unilateral ureteral obstruction (UUO) kidneys and TGF-β induced TECs with FATP2 inhibitor (FATP2i) lipofermata restored the FAO activities and alleviated fibrotic responses both in vivo and in vitro. Moreover, the expression of profibrotic cytokines including TGF-β, connective tissue growth factor (CTGF), fibroblast growth factor (FGF), and platelet-derived growth factor subunit B (PDGFB) were all decreased in FATP2i-treated UUO kidneys. Mechanically, FATP2i can effectively attenuate cell apoptosis and endoplasmic reticulum (ER) stress induced by TGF-β treatment in cultured TECs. Taking together, these findings reveal that FATP2 elicits a profibrotic response to renal interstitial fibrosis by inducing lipid metabolic reprogramming including abnormal FAs uptake and defective FAO in TECs. Nature Publishing Group UK 2020-11-20 /pmc/articles/PMC7679409/ /pubmed/33219209 http://dx.doi.org/10.1038/s41419-020-03199-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Yuting
Yan, Qi
Lv, Mengyue
Song, Kaixin
Dai, Yue
Huang, Yi
Zhang, Le
Zhang, Cuntai
Gao, Hongyu
Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis
title Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis
title_full Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis
title_fullStr Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis
title_full_unstemmed Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis
title_short Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis
title_sort involvement of fatp2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679409/
https://www.ncbi.nlm.nih.gov/pubmed/33219209
http://dx.doi.org/10.1038/s41419-020-03199-x
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