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

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 show an association between KRT5+ cells in human fibrotic lung and 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 the matrisome 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 matrisome restricts KRT5+ cell migration in vitro. Together, our findings demonstrate that changes to the ECM in IPF directly influence KRT5+ cell behaviour and function contributing to remodelling events in the fibrotic niche.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Fibroblast Of Lung

DISEASE(S): Idiopathic Pulmonary Fibrosis

SUBMITTER: Maryline Fresquet

LAB HEAD: Clare Lloyd

PROVIDER: PXD037236 | Pride | 2023-09-28

REPOSITORIES: Pride

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