PTX3 Governs Fibroblast-Epithelial Dynamics in Lung Injury and Repair

Dysfunctional interactions between fibroblasts and epithelial cells contribute to the progression of chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). In this study, we utilized a coculture model of human small airway epithelial cells and fibroblasts to investigate intercellular...

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Bibliographic Details
Published in:bioRxiv 2024-12
Main Authors: Marie-Therese Bammert, Kollak, Ines, Hoffmann, Jan Niclas, Peter, Eva, Schlueter, Holger, Li, Jun, Campos, Alexandre R, Viollet, Coralie, Gantner, Florian, Lize, Muriel, Thomas, Matthew James, Quang-Huy Le
Format: Article
Language:English
Subjects:
Bronchus
Cell interactions
Epithelial cells
Fibroblasts
Fibrosis
Lavage
Lung diseases
Pentraxins
Proteomics
Respiratory tract diseases
Transcriptomics
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Summary:Dysfunctional interactions between fibroblasts and epithelial cells contribute to the progression of chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). In this study, we utilized a coculture model of human small airway epithelial cells and fibroblasts to investigate intercellular communication during disease progression. Our transcriptomic and proteomic profiling reveal that fibroblasts repair epithelial cells in acute injury by boosting epithelial fatty acid metabolism; conversely, they exacerbate epithelial damage in chronic injury scenarios. By delineating regulators involved in these responses, we identified pentraxin 3 (PTX3) as a key antifibrotic factor secreted by fibroblasts in response to acute epithelial injury. Importantly, PTX3 levels are decreased in bronchoalveolar lavage (BAL) samples from IPF patients compared to non-fibrotic controls, indicating a potential link between diminished PTX3 levels and fibrosis progression. Furthermore, adding PTX3 to chronically injured epithelial-fibroblast cocultures mitigated the pro-fibrotic response and restored the epithelial barrier integrity. These findings highlight the dual roles of fibroblasts and the critical function of PTX3 in lung injury and repair, offering insights for therapeutic strategies.Competing Interest StatementAll authors were employed by Boehringer Ingelheim Pharma GmbH & Co KG or by C.H. Boehringer Sohn AG and Co KG. This study was funded by Boehringer Ingelheim Pharma GmbH & Co KG.
DOI:10.1101/2024.12.03.626584