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

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 and Clare M. Lloyd ()
Additional contact information
Richard J. Hewitt: Imperial College London
Franz Puttur: Imperial College London
David C. A. Gaboriau: Imperial College London
Frédéric Fercoq: Cancer Research UK Beatson Institute
Maryline Fresquet: The University of Manchester
William J. Traves: Imperial College London
Laura L. Yates: Imperial College London
Simone A. Walker: Imperial College London
Philip L. Molyneaux: Imperial College London
Samuel V. Kemp: Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust
Andrew G. Nicholson: Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust
Alexandra Rice: Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust
Edward Roberts: Cancer Research UK Beatson Institute
Rachel Lennon: The University of Manchester
Leo M. Carlin: Cancer Research UK Beatson Institute
Adam J. Byrne: Imperial College London
Toby M. Maher: Imperial College London
Clare M. Lloyd: Imperial College London

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41621-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41621-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41621-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().