Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Sep;76(3):888-899.
doi: 10.1002/hep.32328. Epub 2022 Feb 20.

The RSPO-LGR4/5-ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease

Stefano Annunziato  1 , Tianliang Sun  1 , Jan S Tchorz  1
Affiliations
Review

The RSPO-LGR4/5-ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease

Stefano Annunziato et al. Hepatology. 2022 Sep.

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.

PubMed Disclaimer

References

REFERENCES

    1. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9-26.
    1. de Lau W, Peng WC, Gros P, Clevers H. The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength. Genes Dev. 2014;28(4):305-16.
    1. Ober EA, Lemaigre FP. Development of the liver: Insights into organ and tissue morphogenesis. J Hepatol. 2018;68(5):1049-62.
    1. Perugorria MJ, Olaizola P, Labiano I, Esparza-Baquer A, Marzioni M, Marin JJG, et al. Wnt-β-catenin signalling in liver development, health and disease. Nat Rev Gastroenterol Hepatol. 2019;16(2):121-36.
    1. Russell JO, Monga SP. Wnt/β-catenin signaling in liver development, homeostasis, and pathobiology. Annu Rev Pathol. 2018;13:351-78.

MeSH terms

LinkOut - more resources