한빛사논문
- 조회551
Seol Hwa Seo1, Eunhwan Kim1, Minguen Yoon1, Soung-Hoon Lee2, Byung-Hyun Park3 and Kang-Yell Choi1,2,*
1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea. 2CK Regeon Inc, Seoul 03722, Republic of Korea. 3Department of Biochemistry and Molecular Biology, Chonbuk National University Medical School, Jeonbuck 54896, Republic of Korea.
*Corresponding author.
Abstract
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.
논문정보
- Research article
- 2022년 09월 (BRIC 등록일 2022-09-29)
- 국내 연구진
- 생명과학 > 분자생물학
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