Metabolic improvement and liver regeneration by inhibiting CXXC5 function for non-alcoholic steatohepatitis treatment

Seol Hwa Seo, Eunhwan Kim, Minguen Yoon, Soung Hoon Lee, Byung Hyun Park, Kang Yell Choi

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1 Citation (Scopus)


Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that results from multiple metabolic disorders. Considering the complexity of the pathogenesis, the identification of a factor mediating the multiple pathogenic phenotypes of NASH will be important for treatment. In this study, we found that CXXC5, a negative feedback regulator of the Wnt/β-catenin pathway, was overexpressed with suppression of Wnt/β-catenin signaling and its target genes involved in hepatic metabolism in obese-NASH patients. Cxxc5−/− mice were found to be resistant to NASH pathogenesis with metabolic improvements. KY19334, a small molecule that activates the Wnt/β-catenin pathway via interference of the CXXC5-Dvl interaction, reversed the overall pathogenic features of NASH as Cxxc5−/− mice. The improvement in NASH by KY19334 is attributed to its regenerative effects through restorative activation of the suppressed Wnt/β-catenin signaling. Overall, the pronounced metabolic improvements with the stimulation of liver regeneration by interfering with the CXXC5-Dvl interaction provide a therapeutic approach for NASH.

Original languageEnglish
Pages (from-to)1511-1523
Number of pages13
JournalExperimental and Molecular Medicine
Issue number9
Publication statusPublished - 2022 Sept

Bibliographical note

Funding Information:
This work was supported by a grant from the National Research Foundation (NRF), the Ministry of Information and Science and ICT of Korea: 2019R1A2C3002751; 2020M3E5E2040018. S.H.S., E.K., and M.Y. were supported by the BK21 PLUS program.

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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