دورية أكاديمية
Lung extracellular matrix modulates KRT5 + basal cell activity in pulmonary fibrosis.
العنوان: | Lung extracellular matrix modulates KRT5 + basal cell activity in pulmonary fibrosis. |
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المؤلفون: | Hewitt RJ; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK.; Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, SW3 6NP, UK., Puttur F; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK., Gaboriau DCA; Facility for Imaging by Light Microscopy, National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK., Fercoq F; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK., Fresquet M; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK., Traves WJ; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK., Yates LL; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK., Walker SA; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK., Molyneaux PL; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK.; Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, SW3 6NP, UK., Kemp SV; Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, SW3 6NP, UK.; Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, City Campus, Hucknall Road, Nottingham, NG5 1PB, UK., Nicholson AG; Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, SW3 6NP, UK., Rice A; Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, SW3 6NP, UK., Roberts E; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK., Lennon R; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK., Carlin LM; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.; School of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK., Byrne AJ; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK., Maher TM; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK.; Keck Medicine of USC, 1510 San Pablo Street, Los Angeles, CA, 90033, USA., Lloyd CM; National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK. c.lloyd@imperial.ac.uk. |
المصدر: | Nature communications [Nat Commun] 2023 Sep 27; Vol. 14 (1), pp. 6039. Date of Electronic Publication: 2023 Sep 27. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Idiopathic Pulmonary Fibrosis*, Humans ; Extracellular Matrix ; Alveolar Epithelial Cells ; Biological Transport ; Cell Movement ; Keratin-5 |
مستخلص: | 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. (© 2023. Springer Nature Limited.) |
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معلومات مُعتمدة: | 203128/Z/16/Z United Kingdom WT_ Wellcome Trust; P89068 United Kingdom DH_ Department of Health; 23983 United Kingdom CRUK_ Cancer Research UK; A31287 United Kingdom CRUK_ Cancer Research UK; A23983 United Kingdom CRUK_ Cancer Research UK; 104931/Z/14/Z United Kingdom WT_ Wellcome Trust; CDA 13-017 United States HX HSRD VA; United Kingdom WT_ Wellcome Trust; CS-2013-13-017 United Kingdom DH_ Department of Health; 202860/Z/16/Z United Kingdom WT_ Wellcome Trust; 107059/Z/15/Z United Kingdom WT_ Wellcome Trust; BB/L015129/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council |
المشرفين على المادة: | 0 (KRT5 protein, human) 0 (Keratin-5) |
تواريخ الأحداث: | Date Created: 20230927 Date Completed: 20230929 Latest Revision: 20240313 |
رمز التحديث: | 20240313 |
مُعرف محوري في PubMed: | PMC10533905 |
DOI: | 10.1038/s41467-023-41621-y |
PMID: | 37758700 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-023-41621-y |