Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis
文献类型：期刊论文
| 作者 | Huang, He-ming1,3; Fan, Shi-jie1,2; Zhou, Xiao-ru1; Liu, Yan-jun1,3; Li, Xiao1,2; Liao, Li-ping1,2; Huang, Jing1,2; Shi, Cui-cui3; Yu, Liang1 ; Fu, Rong1,3
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2021-08-02 |
| 页码 | 13 |
| 关键词 | nonalcoholic steatohepatitis inflammation histone deacetylase inhibitor givinostat epigenetics |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-021-00725-1 |
| 通讯作者 | Zhang, Yuan-yuan(zhangyy@simm.ac.cn) ; Luo, Cheng(cluo@simm.ac.cn) ; Li, Guang-ming(liguangming@xinhuamed.com.cn) |
| 英文摘要 | Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg center dot kg(-1)center dot d(-1), ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH. |
| WOS关键词 | HEPATIC-FIBROSIS ; KUPFFER CELLS ; DISEASE ; INFLAMMATION ; MACROPHAGES ; MANAGEMENT ; NASH |
| 资助项目 | National Natural Science Foundation of China[81070344] ; National Natural Science Foundation of China[81803554] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[81821005] ; Ministry of Science and Technology of China[2015CB910304] ; National Science & Technology Major Project of China[2018ZX09711002] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000680322000001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/298277]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Yuan-yuan; Luo, Cheng; Li, Guang-ming |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Gastroenterol, Shanghai 200092, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, He-ming,Fan, Shi-jie,Zhou, Xiao-ru,et al. Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis[J]. ACTA PHARMACOLOGICA SINICA,2021:13. |
| APA | Huang, He-ming.,Fan, Shi-jie.,Zhou, Xiao-ru.,Liu, Yan-jun.,Li, Xiao.,...&Li, Guang-ming.(2021).Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis.ACTA PHARMACOLOGICA SINICA,13. |
| MLA | Huang, He-ming,et al."Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis".ACTA PHARMACOLOGICA SINICA (2021):13. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。