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

First Author  Wilson DH Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  445
PubMed ID  31974352 Mgi Jnum  J:284248
Mgi Id  MGI:6387559 Doi  10.1038/s41467-020-14283-3
Citation  Wilson DH, et al. (2020) Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors. Nat Commun 11(1):445
abstractText  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.
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