Mercader 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, Ernest2023-10-092023-10-092023-08-172073-4409https://hdl.handle.net/2445/202706Idiopathic 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.18 p.application/pdfengcc by (c) Mercader Barceló, Josep et al., 2023http://creativecommons.org/licenses/by/3.0/es/Fibrosi pulmonarMitocondrisPulmonary fibrosisMitochondriainfo:eu-repo/semantics/article2023-10-02info:eu-repo/semantics/openAccess37626894