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Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis

Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated...

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Autores principales: Ramil-Gómez, Olalla, Rodríguez-Carmona, Ana, Fernández-Rodríguez, Jennifer Adriana, Pérez-Fontán, Miguel, Ferreiro-Hermida, Tamara, López-Pardo, Mirian, Pérez-López, Teresa, López-Armada, María J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998819/
https://www.ncbi.nlm.nih.gov/pubmed/33805753
http://dx.doi.org/10.3390/antiox10030447
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author Ramil-Gómez, Olalla
Rodríguez-Carmona, Ana
Fernández-Rodríguez, Jennifer Adriana
Pérez-Fontán, Miguel
Ferreiro-Hermida, Tamara
López-Pardo, Mirian
Pérez-López, Teresa
López-Armada, María J.
author_facet Ramil-Gómez, Olalla
Rodríguez-Carmona, Ana
Fernández-Rodríguez, Jennifer Adriana
Pérez-Fontán, Miguel
Ferreiro-Hermida, Tamara
López-Pardo, Mirian
Pérez-López, Teresa
López-Armada, María J.
author_sort Ramil-Gómez, Olalla
collection PubMed
description Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.
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spelling pubmed-79988192021-03-28 Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis Ramil-Gómez, Olalla Rodríguez-Carmona, Ana Fernández-Rodríguez, Jennifer Adriana Pérez-Fontán, Miguel Ferreiro-Hermida, Tamara López-Pardo, Mirian Pérez-López, Teresa López-Armada, María J. Antioxidants (Basel) Article Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane. MDPI 2021-03-13 /pmc/articles/PMC7998819/ /pubmed/33805753 http://dx.doi.org/10.3390/antiox10030447 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Ramil-Gómez, Olalla
Rodríguez-Carmona, Ana
Fernández-Rodríguez, Jennifer Adriana
Pérez-Fontán, Miguel
Ferreiro-Hermida, Tamara
López-Pardo, Mirian
Pérez-López, Teresa
López-Armada, María J.
Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis
title Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis
title_full Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis
title_fullStr Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis
title_full_unstemmed Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis
title_short Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis
title_sort mitochondrial dysfunction plays a relevant role in pathophysiology of peritoneal membrane damage induced by peritoneal dialysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998819/
https://www.ncbi.nlm.nih.gov/pubmed/33805753
http://dx.doi.org/10.3390/antiox10030447
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