Histone deacetylase inhibitor givinostat alleviates liver fibrosis by regulating hepatic stellate cell activation
文献类型：期刊论文
| 作者 | Huang, He-Ming1,2; Zhou, Xiao-Ru2; Liu, Yan-Jun1,2; Fan, Shi-Jie2,3; Liao, Li-Ping2,3; Huang, Jing2,3; Shi, Cui-Cui1; Yu, Liang2 ; Pen, Jin-Jin1,2; Luo, Cheng2,3
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| 刊名 | MOLECULAR MEDICINE REPORTS
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| 出版日期 | 2021-05-01 |
| 卷号 | 23期号:5页码:12 |
| ISSN号 | 1791-2997 |
| 关键词 | liver fibrosis hepatic stellate cell histone deacetylase inhibitor epigenetics givinostat |
| DOI | 10.3892/mmr.2021.11944 |
| 通讯作者 | Shi, Cui-Cui(shicuicui2005@126.com) ; Li, Guang-Ming(liguangming@xinhuamed.com.cn) |
| 英文摘要 | Hepatic fibrosis, a common pathological manifestation of chronic liver injury, is generally considered to be the end result of an increase in extracellular matrix produced by activated hepatic stellate cells (HSCs). The aim of the present study was to target the mechanisms underlying HSC activation in order to provide a powerful therapeutic strategy for the prevention and treatment of liver fibrosis. In the present study, a high-throughput screening assay was established, and the histone deacetylase inhibitor givinostat was identified as a potent inhibitor of HSC activation in vitro. Givinostat significantly inhibited HSC activation in vivo, ameliorated carbon tetrachloride-induced mouse liver fibrosis and lowered plasma aminotransferases. Transcriptomic analysis revealed the most significantly regulated genes in the givinostat treatment group in comparison with those in the solvent group, among which, dermokine (Dmkn), mesothelin (Msln) and uroplakin-3b (Upk3b) were identified as potential regulators of HSC activation. Givinostat significantly reduced the mRNA expression of Dmkn, Msln and Upk3b in both a mouse liver fibrosis model and in HSC-LX2 cells. Knockdown of any of the aforementioned genes inhibited the TGF-beta 1-induced expression of alpha-smooth muscle actin and collagen type I, indicating that they are crucial for HSC activation. In summary, using a novel strategy targeting HSC activation, the present study identified a potential epigenetic drug for the treatment of hepatic fibrosis and revealed novel regulators of HSC activation. |
| 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] ; National Natural Science Foundation of China[81773568] ; Ministry of Science and Technology of China[2015CB910304] ; National Science & Technology Major Project of China[2018ZX09711002] ; Youth Innovation Promotion Association[2017333] |
| WOS研究方向 | Oncology ; Research & Experimental Medicine |
| 语种 | 英语 |
| 出版者 | SPANDIDOS PUBL LTD |
| WOS记录号 | WOS:000631108000001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/295549]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Shi, Cui-Cui; Li, Guang-Ming |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Gastroenterol, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Chem Biol Ctr, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, He-Ming,Zhou, Xiao-Ru,Liu, Yan-Jun,et al. Histone deacetylase inhibitor givinostat alleviates liver fibrosis by regulating hepatic stellate cell activation[J]. MOLECULAR MEDICINE REPORTS,2021,23(5):12. |
| APA | Huang, He-Ming.,Zhou, Xiao-Ru.,Liu, Yan-Jun.,Fan, Shi-Jie.,Liao, Li-Ping.,...&Li, Guang-Ming.(2021).Histone deacetylase inhibitor givinostat alleviates liver fibrosis by regulating hepatic stellate cell activation.MOLECULAR MEDICINE REPORTS,23(5),12. |
| MLA | Huang, He-Ming,et al."Histone deacetylase inhibitor givinostat alleviates liver fibrosis by regulating hepatic stellate cell activation".MOLECULAR MEDICINE REPORTS 23.5(2021):12. |
入库方式： OAI收割
来源：上海药物研究所
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