The Notch signaling pathway plays major roles in organ development across animal species. In the mammalian liver, Notch has been found critical in development, regeneration and disease. In this review, we highlight the major advances in our understanding of the role of Notch activity in proper liver development and function. Specifically, we discuss the latest discoveries on how Notch, in conjunction with other signaling pathways, aids in proper liver development, regeneration and repair. In addition, we review the latest in the role of Notch signaling in the pathogenesis of liver fibrosis and chronic liver disease. Finally, recent evidence has shed light on the emerging connection between Notch signaling and glucose and lipid metabolism. We hope that highlighting the major advances in the roles of Notch signaling in the liver will stimulate further research in this exciting field and generate additional ideas for therapeutic manipulation of the Notch pathway in liver diseases.
Keywords: Alagille syndrome; biliary development; genetic modifiers; liver; liver fibrosis; liver metabolism; liver regeneration; notch signaling.
Conflict of interest statement
The authors declare no conflict of interest. The funders had no role in the design of the study, in the writing of the manuscript or in the decision to publish the manuscript.
Emerging Roles of Notch Signaling in Liver DiseaseF Geisler et al. Hepatology 61 (1), 382-92. PMID 24930574. - ReviewThis review critically discusses the most recent advances in the role of Notch signaling in liver development, homeostasis, and disease. It is now clear that the signific …
Notch Signaling and New Therapeutic Options in Liver DiseaseCM Morell et al. J Hepatol 60 (4), 885-90. PMID 24308992.Notch signaling is a crucial determinant of cell fate decision during development and disease in several organs. Notch effects are strictly dependent on the cellular cont …
Analysis of Liver Repair Mechanisms in Alagille Syndrome and Biliary Atresia Reveals a Role for Notch SignalingL Fabris et al. Am J Pathol 171 (2), 641-53. PMID 17600123.Patients with Alagille syndrome (AGS), a genetic disorder of Notch signaling, suffer from severe ductopenia and cholestasis, but progression to biliary cirrhosis is rare. …
Notch Signalling Beyond Liver Development: Emerging Concepts in Liver Repair and OncogenesisCM Morell et al. Clin Res Hepatol Gastroenterol 37 (5), 447-54. PMID 23806629. - ReviewNotch signalling is an evolutionarily conserved intercellular pathway involved in many aspects of development and tissue renewal in several organs. The importance of Notc …
Novel Insights on Notch Signaling Pathways in Liver FibrosisMM Ni et al. Eur J Pharmacol 826, 66-74. PMID 29501868. - ReviewLiver fibrosis is characterized by an increased and altered deposition of extracellular matrix (ECM) proteins that make up excessive tissue scarring and promote chronic l …
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Does Mechanocrine Signaling by Liver Sinusoidal Endothelial Cells Offer New Opportunities for the Development of Anti-fibrotics?S Soydemir et al. Front Med (Lausanne) 6, 312. PMID 31998732.
Notch Signaling in Kidney Development, Maintenance, and DiseaseM Mukherjee et al. Biomolecules 9 (11). PMID 31690016. - ReviewKidney development involves formation of nephrons intricately aligned with the vasculature and connected to a branched network of collecting ducts. Notch signaling plays …