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

Author

Listed:
  • Richard J. Hewitt

    (Imperial College London
    Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust)

  • 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
    Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust)

  • Samuel V. Kemp

    (Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust
    Nottingham University Hospitals NHS Trust, City Campus)

  • 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
    University of Glasgow)

  • Adam J. Byrne

    (Imperial College London)

  • Toby M. Maher

    (Imperial College London
    Keck Medicine of USC)

  • Clare M. Lloyd

    (Imperial College London)

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.

Suggested 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., 2023. "Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41621-y
    DOI: 10.1038/s41467-023-41621-y
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    References listed on IDEAS

    as
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