Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis.

Aberrant expansion of KRT5+ basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+ cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5+ cells migrate within the fibrotic lung, navigating regional differences in collagen topography. In vitro, KRT5+ cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry- based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5+ cell migration in vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5+ cell behaviour and function contributing to remodelling events in the fibrotic niche. © 2023. Springer Nature Limited.

Citation

Richard J Hewitt, Franz Puttur, David C A Gaboriau, Frédéric Fercoq, Maryline Fresquet, William J Traves, Laura L Yates, Simone A Walker, Philip L Molyneaux, Samuel V Kemp, Andrew G Nicholson, Alexandra Rice, Edward Roberts, Rachel Lennon, Leo M Carlin, Adam J Byrne, Toby M Maher, Clare M Lloyd. Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis. Nature communications. 2023 Sep 27;14(1):6039

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PMID: 37758700

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