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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
    1. Andrew E. Vaughan & Alexis N. Brumwell & Ying Xi & Jeffrey E. Gotts & Doug G. Brownfield & Barbara Treutlein & Kevin Tan & Victor Tan & Feng Chun Liu & Mark R. Looney & Michael A. Matthay & Jason R. R, 2015. "Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury," Nature, Nature, vol. 517(7536), pages 621-625, January.
    2. Riina Kaukonen & Anja Mai & Maria Georgiadou & Markku Saari & Nicola De Franceschi & Timo Betz & Harri Sihto & Sami Ventelä & Laura Elo & Eija Jokitalo & Jukka Westermarck & Pirkko-Liisa Kellokumpu-Le, 2016. "Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    3. Benedikt Jaeger & Jonas Christian Schupp & Linda Plappert & Oliver Terwolbeck & Nataliia Artysh & Gian Kayser & Peggy Engelhard & Taylor Sterling Adams & Robert Zweigerdt & Henning Kempf & Stefan Lien, 2022. "Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Andrew D. Doyle & Nicole Carvajal & Albert Jin & Kazue Matsumoto & Kenneth M. Yamada, 2015. "Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions," Nature Communications, Nature, vol. 6(1), pages 1-15, December.
    5. Huaping Chen & Jing Qu & Xiangwei Huang & Ashish Kurundkar & Lanyan Zhu & Naiheng Yang & Aida Venado & Qiang Ding & Gang Liu & Veena B. Antony & Victor J. Thannickal & Yong Zhou, 2016. "Mechanosensing by the α6-integrin confers an invasive fibroblast phenotype and mediates lung fibrosis," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
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