Tchorz, Jan, Sun, Tianliang and Annunziato, Stefano (2022) The RSPO-LGR4/5-ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease. Hepatology (Baltimore, Md.), 76 (3). pp. 888-899. ISSN 1527-3350

Abstract

WNT/β-catenin signaling plays pivotal roles during liver development, homeostasis, and regeneration. Likewise, its deregulation disturbs metabolic liver zonation and is responsible for the development of a large number of hepatic tumors. Liver fibrosis, which has become a major health burden for society and a hallmark of NASH, can also be promoted by WNT/β-catenin signaling. Upstream regulatory mechanisms controlling hepatic WNT/β-catenin activity may constitute targets for the development of novel therapies addressing these life-threatening conditions. The R-spondin (RSPO)-leucine-rich repeat-containing G protein-coupled receptor (LGR) 4/5-zinc and ring finger (ZNRF) 3/ring finger 43 (RNF43) module is fine-tuning WNT/β-catenin signaling in several tissues and is essential for hepatic WNT/β-catenin activity. In this review article, we recapitulate the role of the RSPO-LGR4/5-ZNRF3/RNF43 module during liver development, homeostasis, metabolic zonation, regeneration, and disease. We further discuss the controversy around LGR5 as a liver stem cell marker.

Item Type:	Article
Keywords:	Homeostasis Liver Receptors, G-Protein-Coupled Thrombospondins Ubiquitin-Protein Ligases Wnt Signaling Pathway beta Catenin
Date Deposited:	14 Aug 2025 00:45
Last Modified:	14 Aug 2025 00:45
URI:	https://oak.novartis.com/id/eprint/43373