TGF-β1-induced deposition of provisional extracellular matrix by tracheal basal cells promotes epithelial-to-mesenchymal transition in a c-Jun NH2 -terminal kinase-1-dependent manner

American Journal of Physiology. Lung Cellular and Molecular Physiology
Jos van der VeldenYvonne M W Janssen-Heininger

Abstract

Epithelial cells have been suggested as potential drivers of lung fibrosis, although the epithelial-dependent pathways that promote fibrogenesis remain unknown. Extracellular matrix is increasingly recognized as an environment that can drive cellular responses in various pulmonary diseases. In this study, we demonstrate that transforming growth factor-β1 (TGF-β1)-stimulated mouse tracheal basal (MTB) cells produce provisional matrix proteins in vitro, which initiate mesenchymal changes in subsequently freshly plated MTB cells via Rho kinase- and c-Jun NH2-terminal kinase (JNK1)-dependent processes. Repopulation of decellularized lung scaffolds, derived from mice with bleomycin-induced fibrosis or from patients with idiopathic pulmonary fibrosis, with wild-type MTB cells resulted in a loss of epithelial gene expression and augmentation of mesenchymal gene expression compared with cells seeded into decellularized normal lungs. In contrast, Jnk1-/- basal cells seeded into fibrotic lung scaffolds retained a robust epithelial expression profile, failed to induce mesenchymal genes, and differentiated into club cell secretory protein-expressing cells. This new paradigm wherein TGF-β1-induced extracellular matrix derived from MTB cells...Continue Reading

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Citations

Dec 21, 2018·International Journal of Molecular Sciences·Andrea PorzionatoRaffaele De Caro
Jun 8, 2018·European Respiratory Review : an Official Journal of the European Respiratory Society·Sarah E Gilpin, Darcy E Wagner
Jul 2, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Josephine C AdamsIrving H Zucker
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Oct 9, 2019·Acta Biomaterialia·Bethany M YoungRebecca L Heise
Feb 26, 2021·Biotechnology and Bioengineering·Seyed Hossein MahfouziSeyed Hamid Safiabadi Tali
Aug 26, 2021·Regenerative Medicine·Seyed Hossein MahfouziGhassem Amoabediny
Jun 16, 2021·American Journal of Respiratory Cell and Molecular Biology·Victoria A PtasinskiLynne A Murray

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Methods Mentioned

BETA
Protein Assay
light microscopy
PCR
confocal microscopy
nucleotide exchange
ELISA
laser capture microdissection

Software Mentioned

Proteome
Scaffold
Proteome Discoverer
SEQUEST
MetaMorph
SPSS

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