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

Mercader-Barceló, Josep ; Martín-Medina, Aina ; Truyols-Vives, Joan ; Escarrer-Garau, Gabriel ; Elowsson, Linda LU ; Montes-Worboys, Ana ; Río-Bocos, Carlos ; Muncunill-Farreny, Josep ; Velasco-Roca, Julio and Cederberg, Anna LU , et al. (2023) In Cells 12(16). p.1-18
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Idiopathic Pulmonary Fibrosis/genetics, Autophagy, Mesenchymal Stem Cells, Mitochondria, Lung
in
Cells
volume
12
issue
16
article number
2084
pages
1 - 18
publisher
MDPI AG
external identifiers
  • scopus:85169152321
  • pmid:37626894
ISSN
2073-4409
DOI
10.3390/cells12162084
language
English
LU publication?
yes
id
88553901-9e48-4ead-a8f2-dfabae31b542
date added to LUP
2023-09-01 11:16:46
date last changed
2024-04-20 02:23:37
@article{88553901-9e48-4ead-a8f2-dfabae31b542,
  abstract     = {{<p>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.</p>}},
  author       = {{Mercader-Barceló, Josep and Martín-Medina, Aina and Truyols-Vives, Joan and Escarrer-Garau, Gabriel and Elowsson, Linda and Montes-Worboys, Ana and Río-Bocos, Carlos and Muncunill-Farreny, Josep and Velasco-Roca, Julio and Cederberg, Anna and Kadefors, Måns and Molina-Molina, Maria and Westergren-Thorsson, Gunilla and Sala-Llinàs, Ernest}},
  issn         = {{2073-4409}},
  keywords     = {{Humans; Idiopathic Pulmonary Fibrosis/genetics; Autophagy; Mesenchymal Stem Cells; Mitochondria; Lung}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{16}},
  pages        = {{1--18}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Mitochondrial Dysfunction in Lung Resident Mesenchymal Stem Cells from Idiopathic Pulmonary Fibrosis Patients}},
  url          = {{http://dx.doi.org/10.3390/cells12162084}},
  doi          = {{10.3390/cells12162084}},
  volume       = {{12}},
  year         = {{2023}},
}