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Publication : NOTCH signalling - a core regulator of bile duct disease?

First Author  Martinez Lyons A Year  2023
Journal  Dis Model Mech Volume  16
Issue  9 PubMed ID  37605966
Mgi Jnum  J:340273 Mgi Id  MGI:7526818
Doi  10.1242/dmm.050231 Citation  Martinez Lyons A, et al. (2023) NOTCH signalling - a core regulator of bile duct disease?. Dis Model Mech 16(9)
abstractText  The Notch signalling pathway is an evolutionarily conserved mechanism of cell-cell communication that mediates cellular proliferation, fate determination and maintenance of stem/progenitor cell populations across tissues. Although it was originally identified as a critical regulator of embryonic liver development, NOTCH signalling activation has been associated with the pathogenesis of a number of paediatric and adult liver diseases. It remains unclear, however, what role NOTCH actually plays in these pathophysiological processes and whether NOTCH activity represents the reactivation of a conserved developmental programme that is essential for adult tissue repair. In this Review, we explore the concepts that NOTCH signalling reactivation in the biliary epithelium is a reiterative and essential response to bile duct damage and that, in disease contexts in which biliary epithelial cells need to be regenerated, NOTCH signalling supports ductular regrowth. Furthermore, we evaluate the recent literature on NOTCH signalling as a critical factor in progenitor-mediated hepatocyte regeneration, which indicates that the mitogenic role for NOTCH signalling in biliary epithelial cell proliferation has also been co-opted to support other forms of epithelial regeneration in the adult liver.
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