Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors.

Autor: Wilson DH; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK., Jarman EJ; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK., Mellin RP; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK.; Infectious Diseases and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia., Wilson ML; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK., Waddell SH; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK., Tsokkou P; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK., Younger NT; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK., Raven A; Cancer Research UK Beatson Institute, Glasgow, UK., Bhalla SR; Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Centre for Cancer Science, Queen's Medical Centre, Nottingham, UK., Noll ATR; Department of Surgery, Maastricht University, Maastricht, The Netherlands., Olde Damink SW; Department of Surgery, Maastricht University, Maastricht, The Netherlands.; Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany., Schaap FG; Department of Surgery, Maastricht University, Maastricht, The Netherlands.; Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany., Chen P; Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA., Bates DO; Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Centre for Cancer Science, Queen's Medical Centre, Nottingham, UK.; COMPARE University of Birmingham and University of Nottingham Midlands, Birmingham, UK., Banales JM; Biodonostia HRI, CIBERehd, Ikerbasque, San Sebastian, Spain., Dean CH; National Heart and Lung Institute, Imperial College London, London, UK., Henderson DJ; Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle, UK., Sansom OJ; Cancer Research UK Beatson Institute, Glasgow, UK.; Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK., Kendall TJ; University of Edinburgh Centre for Inflammation Research, Edinburgh, UK.; Edinburgh Pathology, University of Edinburgh, Edinburgh, UK., Boulter L; MRC Human Genetics Unit, Institute for Genetic and Molecular Medicine, Edinburgh, UK. luke.boulter@ed.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Jan 23; Vol. 11 (1), pp. 445. Date of Electronic Publication: 2020 Jan 23.
DOI: 10.1038/s41467-020-14283-3
Abstrakt: The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration.
Databáze: MEDLINE
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