TY - JOUR T1 - LSC - 2021 - Role of mitochondrial function of lung mesenchymal stem cells in idiopathic pulmonary fibrosis JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA3695 VL - 58 IS - suppl 65 SP - PA3695 AU - Truyols Joan AU - Aina Martin AU - Andreas Jahn AU - Carlos Rio AU - Ernest Sala AU - Josep Mercader Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA3695.abstract N2 - Mesenchymal stem cells (MSC) play a role in tissue repair. However, the role of lung MSC (LMSC) in idiopathic pulmonary fibrosis (IPF) remains to be elucidated. Preliminary results revealed that IPF vs non-IPF LMSC present an impaired repair ability and, under TGF-ß stimulus, an increased migration activity and decreased proliferation. Moreover, microarray gene expression analysis showed that oxidative phosphorylation is the most altered pathway in the IPF LMSC. Here, we aimed to analyse mitochondrial function-related features, the repair activity in pro-fibrotic conditions, and the underlying molecular mechanisms elicited by TGF-ß in IPF LMSC.RT-PCR was used to validate gene expression differences. Mitochondria number was estimated by DNA quantification using ddPCR. Mitochondrial integrity was assessed by TMRM assay. Scratch assays were performed in both direct and indirect coculture with A549 cells.As compared to non-IPF MSC, IPF LMSC presented a lower COX-IV and PINK1 expression and there were no differences in mitochondria number and integrity. However, TGF-ß decreased mitochondrial integrity in IPF LMSC. IPF LMSC showed a delayed repair activity and, in the indirect coculture, TGF-ß preincubation stimulated wound healing more potently in the IPF group. TGF-ß-treated IPF LMSC presented lower COX-IV, ATP6 and PINK1 mRNA levels than non-IPF LMSC. TGF-ß treatment induced the expression of the migration marker VEGF.The impaired repair activity in IPF LSMC was associated with signs of mitochondrial dysfunction. IPF LMSC seem to be more sensitive to TGF-ß. TGF-ß, in turn, induces mitochondrial dysfunction in IPF MSC. Collectively, these results suggest that the overproduction of TGF-ß in IPF may alter LMSC function by promoting mitochondrial dysfunction.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3695.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -