Your browser doesn't support javascript.
loading
Notch-IGF1 signaling during liver regeneration drives biliary epithelial cell expansion and inhibits hepatocyte differentiation.
Minnis-Lyons, Sarah E; Ferreira-González, Sofía; Aleksieva, Niya; Man, Tak Yung; Gadd, Victoria L; Williams, Michael J; Guest, Rachel V; Lu, Wei-Yu; Dwyer, Benjamin J; Jamieson, Tam; Nixon, Colin; Van Hul, Noemi; Lemaigre, Frederic P; McCafferty, John; Leclercq, Isabelle A; Sansom, Owen J; Boulter, Luke; Forbes, Stuart J.
Afiliación
  • Minnis-Lyons SE; Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, Edinburgh, UK.
  • Ferreira-González S; Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, Edinburgh, UK.
  • Aleksieva N; Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, Edinburgh, UK.
  • Man TY; Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, Edinburgh, UK.
  • Gadd VL; Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, Edinburgh, UK.
  • Williams MJ; Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, Edinburgh, UK.
  • Guest RV; Clinical Surgery, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK.
  • Lu WY; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Dwyer BJ; Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, Edinburgh, UK.
  • Jamieson T; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, UK.
  • Nixon C; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, UK.
  • Van Hul N; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
  • Lemaigre FP; Université catholique de Louvain, de Duve Institute, Brussels, Belgium.
  • McCafferty J; IONTAS Ltd., Iconix Park, London Road, Pampisford, Cambridgeshire, UK.
  • Leclercq IA; Laboratory of Gastroenterology, Université Catholique de Louvain, Brussels, Belgium.
  • Sansom OJ; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, UK.
  • Boulter L; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, UK.
  • Forbes SJ; MRC Human Genetics Unit, Institute of Genetics and Cancer, Edinburgh, UK. stuart.forbes@ed.ac.uk luke.boulter@ed.ac.uk.
Sci Signal ; 14(688)2021 06 22.
Article en En | MEDLINE | ID: mdl-34158399
In the adult liver, a population of facultative progenitor cells called biliary epithelial cells (BECs) proliferate and differentiate into cholangiocytes and hepatocytes after injury, thereby restoring liver function. In mammalian models of chronic liver injury, Notch signaling is essential for bile duct formation from these cells. However, the continual proliferation of BECs and differentiation of hepatocytes in these models have limited their use for determining whether Notch signaling is required for BECs to replenish hepatocytes after injury in the mammalian liver. Here, we used a temporally restricted model of hepatic repair in which large-scale hepatocyte injury and regeneration are initiated through the acute loss of Mdm2 in hepatocytes, resulting in the rapid, coordinated proliferation of BECs. We found that transient, early activation of Notch1- and Notch3-mediated signaling and entrance into the cell cycle preceded the phenotypic expansion of BECs into hepatocytes. Notch inhibition reduced BEC proliferation, which resulted in failure of BECs to differentiate into hepatocytes, indicating that Notch-dependent expansion of BECs is essential for hepatocyte regeneration. Notch signaling increased the abundance of the insulin-like growth factor 1 receptor (IGF1R) in BECs, and activating IGFR signaling increased BEC numbers but suppressed BEC differentiation into hepatocytes. These results suggest that different signaling mechanisms control BEC expansion and hepatocyte differentiation.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor I del Crecimiento Similar a la Insulina / Regeneración Hepática Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor I del Crecimiento Similar a la Insulina / Regeneración Hepática Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos