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, Josep, Martín-Medina, Aina, Truyols-Vives, Joan, Escarrer-Garau, Gabriel, Elowsson, Linda, Montes-Worboys, Ana, Rio-Bocos, Carlos, Muncunill Farreny, Josep, Velasco, Julio, Cederberg, Anna, Kadefors, Måns, Molina-Molina, Maria, Westergren-Thorsson, Gunilla, Sala Llinas, Ernest
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/19946
Acceso en línea:https://hdl.handle.net/20.500.13003/19946
Access Level:acceso abierto
Palabra clave:Lung
Mitochondria
Idiopathic Pulmonary Fibrosis
Mesenchymal Stem Cells
Humans
Autophagy
Humanos
Autofagia
Células Madre Mesenquimatosas
Pulmón
Fibrosis Pulmonar Idiopática
Mitocondrias
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spelling Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis PatientsMercader, JosepMartín-Medina, AinaTruyols-Vives, JoanEscarrer-Garau, GabrielElowsson, LindaMontes-Worboys, AnaRio-Bocos, CarlosMuncunill Farreny, JosepVelasco, JulioCederberg, AnnaKadefors, MånsMolina-Molina, MariaWestergren-Thorsson, GunillaSala Llinas, ErnestLungMitochondriaIdiopathic Pulmonary FibrosisMesenchymal Stem CellsHumansAutophagyHumanosAutofagiaCélulas Madre MesenquimatosasPulmónFibrosis Pulmonar IdiopáticaMitocondriasIdiopathic 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 TGFβ-exposed LRMSC presented different expression profiles of mitochondrial-related genes compared to CON TGFβ-treated cells, suggesting that TGFβ 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.MDPI20232023-08-1720232023-08-17research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/19946reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/199462026-06-22T12:44:07Z
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, Josep
Lung
Mitochondria
Idiopathic Pulmonary Fibrosis
Mesenchymal Stem Cells
Humans
Autophagy
Humanos
Autofagia
Células Madre Mesenquimatosas
Pulmón
Fibrosis Pulmonar Idiopática
Mitocondrias
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, Josep
Martín-Medina, Aina
Truyols-Vives, Joan
Escarrer-Garau, Gabriel
Elowsson, Linda
Montes-Worboys, Ana
Rio-Bocos, Carlos
Muncunill Farreny, Josep
Velasco, Julio
Cederberg, Anna
Kadefors, Måns
Molina-Molina, Maria
Westergren-Thorsson, Gunilla
Sala Llinas, Ernest
author Mercader, Josep
author_facet Mercader, Josep
Martín-Medina, Aina
Truyols-Vives, Joan
Escarrer-Garau, Gabriel
Elowsson, Linda
Montes-Worboys, Ana
Rio-Bocos, Carlos
Muncunill Farreny, Josep
Velasco, Julio
Cederberg, Anna
Kadefors, Måns
Molina-Molina, Maria
Westergren-Thorsson, Gunilla
Sala Llinas, Ernest
author_role author
author2 Martín-Medina, Aina
Truyols-Vives, Joan
Escarrer-Garau, Gabriel
Elowsson, Linda
Montes-Worboys, Ana
Rio-Bocos, Carlos
Muncunill Farreny, Josep
Velasco, Julio
Cederberg, Anna
Kadefors, Måns
Molina-Molina, Maria
Westergren-Thorsson, Gunilla
Sala Llinas, Ernest
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Lung
Mitochondria
Idiopathic Pulmonary Fibrosis
Mesenchymal Stem Cells
Humans
Autophagy
Humanos
Autofagia
Células Madre Mesenquimatosas
Pulmón
Fibrosis Pulmonar Idiopática
Mitocondrias
topic Lung
Mitochondria
Idiopathic Pulmonary Fibrosis
Mesenchymal Stem Cells
Humans
Autophagy
Humanos
Autofagia
Células Madre Mesenquimatosas
Pulmón
Fibrosis Pulmonar Idiopática
Mitocondrias
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 TGFβ-exposed LRMSC presented different expression profiles of mitochondrial-related genes compared to CON TGFβ-treated cells, suggesting that TGFβ 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
2023-08-17
2023
2023-08-17
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/19946
url https://hdl.handle.net/20.500.13003/19946
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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