机构：[1]Department of Clinical Laboratory, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.[2]Department of Clinical Laboratory, Kunshan First People's Hospital, Jiangsu University, Kunshan, 215300, China.[3]Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.
Whether vitamin D (VD3) supplementation is associated with improved liver fibrosis is controversial.Liver fibrosis models were treated with VD3, active VD (1,25-OH2 Vitamin D3), or collaboration with GSK126 (Ezh2 inhibitor) respectively. Hepatic stellate cells (HSCs) were co-cultured with hepatocytes and then, stimulated with TGF-β. Autophagy of hepatocytes was determined after the intervention of 1,25-OH2 Vitamin D3 and GSK126. Also, the active status of HSCs and the mechanism with 1,25-OH2 Vitamin D3 and GSK126 intervention were detected.1,25-OH2 Vitamin D3, but not vitamin D3, is involved in anti-fibrosis and partially improves liver function, which might be associated with related enzymes and receptors (especially CYP2R1), leading to decreased of its biotransformation. GSK126 plays a synergistic role in anti-fibrosis. The co-culture system showed increased hepatocyte autophagy after HSCs activation. Supplementation with 1,25-OH2 Vitamin D3 or combined GSK126 reduced these effects. Further studies showed that 1,25-OH2 Vitamin D3 promoted H3K27 methylation of DKK1 promoter through VDR/Ezh2 due to the weakening for HSCs inhibitory signal.VD3 bioactive form 1,25-OH2 Vitamin D3 is responsible for the anti-fibrosis, which might have bidirectional effects on HSCs by regulating histone modification. The inhibitor of Ezh2 plays a synergistic role in this process.This article is protected by copyright. All rights reserved.
基金：
This study was supported by the National Natural Science Foundation of China (grant
numbers 81672083, 82070730) and the Suzhou Health Youth Backbone Talent of National Mentor
System (grant number Qngg2021043).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|3 区胃肠肝病学
最新[2025]版：
大类|3 区医学
小类|3 区胃肠肝病学
第一作者：
第一作者机构：[1]Department of Clinical Laboratory, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.[2]Department of Clinical Laboratory, Kunshan First People's Hospital, Jiangsu University, Kunshan, 215300, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Clinical Laboratory, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.[3]Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.[*1]Department of Clinical Laboratory, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.[*2]Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China.
推荐引用方式(GB/T 7714)：
Zhang Qinghui,Jia Rongrong,Chen Minjie,et al.Antagonizing EZH2 combined with vitamin D3 exerts a synergistic role in anti-fibrosis through bidirectional effects on hepatocytes and HSCs[J].Journal of gastroenterology and hepatology.2023,doi:10.1111/jgh.16126.
APA：
Zhang Qinghui,Jia Rongrong,Chen Minjie,Wang Jianjun,Huang Feng...&Xu Ling.(2023).Antagonizing EZH2 combined with vitamin D3 exerts a synergistic role in anti-fibrosis through bidirectional effects on hepatocytes and HSCs.Journal of gastroenterology and hepatology,,
MLA：
Zhang Qinghui,et al."Antagonizing EZH2 combined with vitamin D3 exerts a synergistic role in anti-fibrosis through bidirectional effects on hepatocytes and HSCs".Journal of gastroenterology and hepatology .(2023)
