Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients

Idiopathic pulmonary fibrosis (IPF) is characterized by an aberrant repair response with uncontrolled turnover of extracellular matrix involving mesenchymal cell phenotypes, where lung resident mesenchymal stem cells (LRMSC) have been supposed to have an important role. However, the contribution of...

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Autores: Mercader Barceló, Josep, Martín Medina, Aina, Truyols Vives, Joan, Escarrer Garau, Gabriel, Elowsson Rendin, Linda, Montes Worboys, Ana, Río Bocos, Carlos, Muncunill Farreny, Josep, Velasco Roca, Julio, Cederberg, Anna, Kadefors, Måns, Molina Molina, María, Westergren-Thorsson, Gunilla, Sala Llinàs, Ernest
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/202706
Acesso em linha:https://hdl.handle.net/2445/202706
Access Level:acceso abierto
Palavra-chave:Fibrosi pulmonar
Mitocondris
Pulmonary fibrosis
Mitochondria
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spelling Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis PatientsMercader Barceló, JosepMartín Medina, AinaTruyols Vives, JoanEscarrer Garau, GabrielElowsson Rendin, LindaMontes Worboys, AnaRío Bocos, CarlosMuncunill Farreny, JosepVelasco Roca, JulioCederberg, AnnaKadefors, MånsMolina Molina, MaríaWestergren-Thorsson, GunillaSala Llinàs, ErnestFibrosi pulmonarMitocondrisPulmonary fibrosisMitochondriaIdiopathic pulmonary fibrosis (IPF) is characterized by an aberrant repair response with uncontrolled turnover of extracellular matrix involving mesenchymal cell phenotypes, where lung resident mesenchymal stem cells (LRMSC) have been supposed to have an important role. However, the contribution of LRMSC in lung fibrosis is not fully understood, and the role of LRMSC in IPF remains to be elucidated. Here, we performed transcriptomic and functional analyses on LRMSC isolated from IPF and control patients (CON). Both over-representation and gene set enrichment analyses indicated that oxidative phosphorylation is the major dysregulated pathway in IPF LRMSC. The most relevant differences in biological processes included complement activation, mesenchyme development, and aerobic electron transport chain. Compared to CON LRMSC, IPF cells displayed impaired mitochondrial respiration, lower expression of genes involved in mitochondrial dynamics, and dysmorphic mitochondria. These changes were linked to an impaired autophagic response and a lower mRNA expression of pro-apoptotic genes. In addition, IPF TGF beta-exposed LRMSC presented different expression profiles of mitochondrial-related genes compared to CON TGF beta-treated cells, suggesting that TGF beta reinforces mitochondrial dysfunction. In conclusion, these results suggest that mitochondrial dysfunction is a major event in LRMSC and that their occurrence might limit LRMSC function, thereby contributing to IPF development.MDPI AG2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/202706Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/cells12162084Cells, 2023, vol. 12, num. 16https://doi.org/10.3390/cells12162084cc by (c) Mercader Barceló, Josep et al., 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2027062026-05-27T06:46:51Z
dc.title.none.fl_str_mv Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
title Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
spellingShingle Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
Mercader Barceló, Josep
Fibrosi pulmonar
Mitocondris
Pulmonary fibrosis
Mitochondria
title_short Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
title_full Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
title_fullStr Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
title_full_unstemmed Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
title_sort Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients
dc.creator.none.fl_str_mv Mercader Barceló, Josep
Martín Medina, Aina
Truyols Vives, Joan
Escarrer Garau, Gabriel
Elowsson Rendin, Linda
Montes Worboys, Ana
Río Bocos, Carlos
Muncunill Farreny, Josep
Velasco Roca, Julio
Cederberg, Anna
Kadefors, Måns
Molina Molina, María
Westergren-Thorsson, Gunilla
Sala Llinàs, Ernest
author Mercader Barceló, Josep
author_facet Mercader Barceló, Josep
Martín Medina, Aina
Truyols Vives, Joan
Escarrer Garau, Gabriel
Elowsson Rendin, Linda
Montes Worboys, Ana
Río Bocos, Carlos
Muncunill Farreny, Josep
Velasco Roca, Julio
Cederberg, Anna
Kadefors, Måns
Molina Molina, María
Westergren-Thorsson, Gunilla
Sala Llinàs, Ernest
author_role author
author2 Martín Medina, Aina
Truyols Vives, Joan
Escarrer Garau, Gabriel
Elowsson Rendin, Linda
Montes Worboys, Ana
Río Bocos, Carlos
Muncunill Farreny, Josep
Velasco Roca, Julio
Cederberg, Anna
Kadefors, Måns
Molina Molina, María
Westergren-Thorsson, Gunilla
Sala Llinàs, Ernest
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fibrosi pulmonar
Mitocondris
Pulmonary fibrosis
Mitochondria
topic Fibrosi pulmonar
Mitocondris
Pulmonary fibrosis
Mitochondria
description Idiopathic pulmonary fibrosis (IPF) is characterized by an aberrant repair response with uncontrolled turnover of extracellular matrix involving mesenchymal cell phenotypes, where lung resident mesenchymal stem cells (LRMSC) have been supposed to have an important role. However, the contribution of LRMSC in lung fibrosis is not fully understood, and the role of LRMSC in IPF remains to be elucidated. Here, we performed transcriptomic and functional analyses on LRMSC isolated from IPF and control patients (CON). Both over-representation and gene set enrichment analyses indicated that oxidative phosphorylation is the major dysregulated pathway in IPF LRMSC. The most relevant differences in biological processes included complement activation, mesenchyme development, and aerobic electron transport chain. Compared to CON LRMSC, IPF cells displayed impaired mitochondrial respiration, lower expression of genes involved in mitochondrial dynamics, and dysmorphic mitochondria. These changes were linked to an impaired autophagic response and a lower mRNA expression of pro-apoptotic genes. In addition, IPF TGF beta-exposed LRMSC presented different expression profiles of mitochondrial-related genes compared to CON TGF beta-treated cells, suggesting that TGF beta reinforces mitochondrial dysfunction. In conclusion, these results suggest that mitochondrial dysfunction is a major event in LRMSC and that their occurrence might limit LRMSC function, thereby contributing to IPF development.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/202706
url https://hdl.handle.net/2445/202706
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cells12162084
Cells, 2023, vol. 12, num. 16
https://doi.org/10.3390/cells12162084
dc.rights.none.fl_str_mv cc by (c) Mercader Barceló, Josep et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Mercader Barceló, Josep et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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