Journal
LIVER RESEARCH
Volume 6, Issue 3, Pages 139-145Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.livres.2022.09.002
Keywords
Roof plate-specific spondin (RSPO); Leucine-rich repeat-containing G-protein-coupled receptor (LGR); Zinc and ring finger 3 (ZNRF3); Ring finger protein 43 (RNF43); WNT signaling pathway; Liver homeostasis; Liver fibrosis; Liver cancer
Categories
Funding
- Scienti fic Research Common Program of Beijing Municipal Commission of Education [82070623]
- National Natural Science Foundation of China [81970532, 7202007]
- Beijing Natural Science Foundation
- [KM202010025029]
Ask authors/readers for more resources
RSPOs are evolutionarily conserved signals that play important roles in liver homeostasis and disease by interacting with different receptors and regulating multiple signaling pathways. They enhance WNT signaling, promote cell proliferation, protect hepatocytes, improve liver regenerative potential, and affect liver metabolic zonation.
As evolutionarily conserved signals, roof plate-specific spondins (R-spondins; RSPOs) are a family with four members (RSPO1-4) exerting distinctly different functions. RSPOs have five receptors and correlate with different signaling pathways through these receptors and then perform various functions. Moreover, their best-known molecular function is the capacity to enhance WNT signaling pathways, which play critical roles in several processes. A recent study shows that RSPOs not only potentiate the WNT/beta (b)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling pathway. RSPOs influence liver homeostasis and the development of multiple liver diseases. RSPO1 increases cell proliferation, protects hepatocytes from injury, improves liver regenerative potential, and affects liver metabolic zonation. RSPO2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/b-catenin signaling pathway. RSPO3 is a key determinant of proper liver function, such as promoting hepatocyte regeneration and maintaining liver zonation. RSPO3 is upregulated in liver fibrosis and livers of patients with nonalcoholic steatohepatitis. Besides, RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver cancer. The role of RSPO4 in the liver remains unclear. In this review, the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.& COPY; 2022 The Third Affiliated Hospital of Sun Yat-sen University. Publishing services by Elsevier B. V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available