Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury
Background/Aims: Fatty acid oxidation (FAO), the main source of energy produced by tubular epithelial cells in the kidney, was found to be defective in tubulo-interstitial samples dissected out in kidney biopsies from patients with chronic kidney disease (CKD). Experimental data indicated that this...
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Cell Physiol Biochem Press GmbH & Co KG
2018-06-01
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doaj-484b1a0eb9894756ab3a2480ea1e9f5e2020-11-24T21:26:38ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-06-014741338135110.1159/000490819490819Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney InjuryAurélien BataillePierre GalichonNadjim ChelghoumBadreddine Mohand OumoussaMarie-Julia ZiliotisIman SadiaSophie VandermeerschNoémie Simon-TillauxDavid LegouisRaphaël CohenYi-Chun Xu-DuboisMorgane CommereucEric RondeauStéphane Le CromAlexandre HertigBackground/Aims: Fatty acid oxidation (FAO), the main source of energy produced by tubular epithelial cells in the kidney, was found to be defective in tubulo-interstitial samples dissected out in kidney biopsies from patients with chronic kidney disease (CKD). Experimental data indicated that this decrease was a strong determinant of renal fibrogenesis, hence a focus for therapeutic interventions. Nevertheless, whether persistently differentiated renal tubules, surviving in a pro-fibrotic environment, also suffer from a decrease in FAO, is currently unknown. Methods: To address this question, we isolated proximal tubules captured ex vivo on the basis of the expression of an intact brush border antigen (Prominin-1) in C57BL6/J mice subjected to a controlled, two-hit model of renal fibrosis (reversible ischemic acute kidney injury (AKI) or sham surgery, followed by angiotensin 2 administration). A transcriptomic high throughput sequencing was performed on total mRNA from these cells, and on whole kidneys. Results: In contrast to mice subjected to sham surgery, mice with a history of AKI displayed histologically more renal fibrosis when exposed to angiotensin 2. High throughput RNA sequencing, principal component analysis and clustering showed marked consistency within experimental groups. As expected, FAO transcripts were decreased in whole fibrotic kidneys. Surprisingly, however, up- rather than down-regulation of metabolic pathways (oxidative phosphorylation, fatty acid metabolism, glycolysis, and PPAR signalling pathway) was a hallmark of the differentiated tubules captured from fibrotic kidneys. Immunofluorescence co-staining analysis confirmed that the expression of FAO enzymes was dependent of tubular trophicity. Conclusions: These data suggest that in differentiated proximal tubules energetic hyperactivity is promoted concurrently with organ fibrogenesis.https://www.karger.com/Article/FullText/490819Acute Kidney InjuryEpitheliumFibrosisChronic Kidney DiseaseFatty Acid Oxidation |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aurélien Bataille Pierre Galichon Nadjim Chelghoum Badreddine Mohand Oumoussa Marie-Julia Ziliotis Iman Sadia Sophie Vandermeersch Noémie Simon-Tillaux David Legouis Raphaël Cohen Yi-Chun Xu-Dubois Morgane Commereuc Eric Rondeau Stéphane Le Crom Alexandre Hertig |
spellingShingle |
Aurélien Bataille Pierre Galichon Nadjim Chelghoum Badreddine Mohand Oumoussa Marie-Julia Ziliotis Iman Sadia Sophie Vandermeersch Noémie Simon-Tillaux David Legouis Raphaël Cohen Yi-Chun Xu-Dubois Morgane Commereuc Eric Rondeau Stéphane Le Crom Alexandre Hertig Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury Cellular Physiology and Biochemistry Acute Kidney Injury Epithelium Fibrosis Chronic Kidney Disease Fatty Acid Oxidation |
author_facet |
Aurélien Bataille Pierre Galichon Nadjim Chelghoum Badreddine Mohand Oumoussa Marie-Julia Ziliotis Iman Sadia Sophie Vandermeersch Noémie Simon-Tillaux David Legouis Raphaël Cohen Yi-Chun Xu-Dubois Morgane Commereuc Eric Rondeau Stéphane Le Crom Alexandre Hertig |
author_sort |
Aurélien Bataille |
title |
Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury |
title_short |
Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury |
title_full |
Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury |
title_fullStr |
Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury |
title_full_unstemmed |
Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury |
title_sort |
increased fatty acid oxidation in differentiated proximal tubular cells surviving a reversible episode of acute kidney injury |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2018-06-01 |
description |
Background/Aims: Fatty acid oxidation (FAO), the main source of energy produced by tubular epithelial cells in the kidney, was found to be defective in tubulo-interstitial samples dissected out in kidney biopsies from patients with chronic kidney disease (CKD). Experimental data indicated that this decrease was a strong determinant of renal fibrogenesis, hence a focus for therapeutic interventions. Nevertheless, whether persistently differentiated renal tubules, surviving in a pro-fibrotic environment, also suffer from a decrease in FAO, is currently unknown. Methods: To address this question, we isolated proximal tubules captured ex vivo on the basis of the expression of an intact brush border antigen (Prominin-1) in C57BL6/J mice subjected to a controlled, two-hit model of renal fibrosis (reversible ischemic acute kidney injury (AKI) or sham surgery, followed by angiotensin 2 administration). A transcriptomic high throughput sequencing was performed on total mRNA from these cells, and on whole kidneys. Results: In contrast to mice subjected to sham surgery, mice with a history of AKI displayed histologically more renal fibrosis when exposed to angiotensin 2. High throughput RNA sequencing, principal component analysis and clustering showed marked consistency within experimental groups. As expected, FAO transcripts were decreased in whole fibrotic kidneys. Surprisingly, however, up- rather than down-regulation of metabolic pathways (oxidative phosphorylation, fatty acid metabolism, glycolysis, and PPAR signalling pathway) was a hallmark of the differentiated tubules captured from fibrotic kidneys. Immunofluorescence co-staining analysis confirmed that the expression of FAO enzymes was dependent of tubular trophicity. Conclusions: These data suggest that in differentiated proximal tubules energetic hyperactivity is promoted concurrently with organ fibrogenesis. |
topic |
Acute Kidney Injury Epithelium Fibrosis Chronic Kidney Disease Fatty Acid Oxidation |
url |
https://www.karger.com/Article/FullText/490819 |
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