Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors
| Autor: | S. W. M. Olde Damink, Owen J. Sansom, Charlotte H. Dean, S. H. Waddell, Luke Boulter, David H. Wilson, Ping Chen, Jesus M. Banales, M. L. Wilson, S. R. Bhalla, A. T. R. Noll, Frank G. Schaap, Deborah J. Henderson, Timothy J. Kendall, N. T. Younger, Edward J. Jarman, David O. Bates, P. Tsokkou, R. P. Mellin, Alexander Raven |
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| Přispěvatelé: | RS: NUTRIM - R2 - Liver and digestive health, Surgery, MUMC+: MA Heelkunde (9) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Physiology MAP Kinase Kinase 4 Pyridines medicine.medical_treatment TISSUE GROWTH-FACTOR General Physics and Astronomy Scars Liver transplantation vangl2 phosphorylation Biliary disease stem-cells 0302 clinical medicine Biliary tract disease Cell polarity Medicine Receptor lcsh:Science Wnt Signaling Pathway Multidisciplinary Bile duct Cell Polarity 3. Good health Multidisciplinary Sciences liver-injury medicine.anatomical_structure 030220 oncology & carcinogenesis Science & Technology - Other Topics medicine.symptom Science Cholangitis Sclerosing Mice Transgenic Nerve Tissue Proteins Bile Duct Diseases digestive system General Biochemistry Genetics and Molecular Biology Article Morphogen signalling Wnt-5a Protein 03 medical and health sciences Cicatrix Axin Protein Animals Humans REPAIR Science & Technology model business.industry pathway MUTATIONS Regeneration (biology) fibrosis COMPONENTS JNK Mitogen-Activated Protein Kinases Epithelial Cells General Chemistry medicine.disease Disease Models Animal 030104 developmental biology Cancer research lcsh:Q Liver function Bile Ducts business |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications, 11(1):445. Nature Publishing Group Nature Communications Wilson, D H, Jarman, E J, Mellin, R P, Wilson, M L, Waddell, S, Tsokkou, P, Younger, N T, Raven, A, Bhalla, S R, Noll, A T R, Olde Damink, S W, Schaap, F G, Chen, P, Bates, D O, Banales, J M, Dean, C H, Henderson, D J, Sansom, O J, Kendall, T J & Boulter, L 2020, ' Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors ', Nature Communications, vol. 11, 445 . https://doi.org/10.1038/s41467-020-14283-3 |
| ISSN: | 2041-1723 |
| Popis: | 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. In fibrotic biliary disease, portal fibroblasts promote both biliary scarring and bile duct regeneration. Here, the authors report that the non-canonical Wnt-PCP signalling promotes bile duct scarring in mice, and inhibition of Wnt-ligands reduces the scarring without impairing regeneration. |
| Databáze: | OpenAIRE |
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