Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.12.16.520808v1?rss=1

Authors: Hewitt, R. J., Puttur, F., Gaboriau, D. C. A., Fercoq, F., Fresquet, M., Traves, W. J., Yates, L. L., Walker, S. A., Molyneaux, P. L., Kemp, S. V., Nicholson, A. G., Rice, A., Lennon, R., Carlin, L. M., Byrne, A. J., Maher, T. M., Lloyd, C. M.

Abstract:
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.

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