The role of roof plate-specific spondins in liver homeostasis and disease  

作　　者：Le Yang Wenhui Yue Hang Zhang Yue Gao Lin Yang Liying Li 

机构地区：[1]Department of Cell Biology,Municipal Laboratory for Liver Protection and Regulation of Regeneration,Capital Medical University,Beijing,China

出　　处：《Liver Research》2022年第3期139-145,共7页肝脏研究（英文）

基　　金：This work was supported by grants from the Scientific Research Common Program of Beijing Municipal Commission of Education(No.KM202010025029);the National Natural Science Foundation of China(No.82070623 and 81970532);the Beijing Natural Science Foundation(No.7202007).

摘　　要：As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)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.

关 键 词：Roof plate-specific spondin(RSPO) Leucine-rich repeat-containing G-proteincoupled receptor(LGR) Zinc and ring finger 3(ZNRF3) Ring finger protein 43(RNF43) WNT signaling pathway Liver homeostasis Liver fibrosis Liver cancer 

分 类 号：R575[医药卫生—消化系统]