The RSPO-LGR4/5-ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease
Stefano Annunziato1, Tianliang Sun1, Jan S Tchorz1
1Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Hepatology (Baltimore, Md.)
|January 10, 2022
Summary
The R-spondin-leucine-rich repeat-containing G protein-coupled receptor (RSPO-LGR) module regulates WNT/β-catenin signaling in the liver. This pathway is crucial for liver health, development, and disease, offering potential therapeutic targets.
Area of Science:
- Hepatology
- Molecular Biology
- Cell Signaling
Background:
- WNT/β-catenin signaling is vital for liver development, homeostasis, and regeneration.
- Deregulation of this pathway contributes to metabolic liver zonation disorders, hepatic tumors, and liver fibrosis in non-alcoholic steatohepatitis (NASH).
- Targeting upstream regulators of hepatic WNT/β-catenin activity presents opportunities for novel therapies.
Purpose of the Study:
- To review the function of 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 in the liver.
- To explore the module's role in liver development, homeostasis, metabolic zonation, regeneration, and disease.
- To discuss the debated role of LGR5 as a liver stem cell marker.
Main Methods:
- Literature review of the RSPO-LGR-ZNRF/RNF43 signaling module in the liver.
- Synthesis of current knowledge on WNT/β-catenin pathway regulation in hepatic contexts.
- Analysis of the module's involvement in liver physiology and pathology.
Main Results:
- The RSPO-LGR4/5-ZNRF3/RNF43 module is essential for fine-tuning hepatic WNT/β-catenin signaling.
- This module influences liver development, homeostasis, metabolic zonation, and regeneration.
- Dysregulation of this module is implicated in liver diseases, including fibrosis and tumorigenesis.
Conclusions:
- The RSPO-LGR-ZNRF/RNF43 module is a key regulator of WNT/β-catenin signaling with significant implications for liver health and disease.
- Understanding this module's intricate functions can guide the development of targeted therapies for liver conditions.
- Further research is needed to clarify the precise role of LGR5 in liver stem cell biology.
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