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Selective bromodomain and extra-terminal bromodomain inhibitor inactivates macrophages and hepatic stellate cells to inhibit liver inflammation and fibrosis

文献类型：期刊论文

作者Fu, Rong1,2; Zu, Shi-Jia2,3; Liu, Yan-Jun1,2; Li, Jia-Cheng2; Dang, Wen-Zhen2; Liao, Li-Ping2; Liu, Li-Ping2; Chen, Pan-Yu2; Huang, He-Ming2; Wu, Kang-Hui1,2
刊名BIOENGINEERED
出版日期2022-04-01
卷号13期号:4页码:10914-10930
ISSN号2165-5979
关键词BET inhibitor macrophage hepatic stellate cell inflammation fibrosis
DOI10.1080/21655979.2022.2066756
通讯作者Li, Guang-Ming(ligm68@126.com)
英文摘要Liver fibrosis occurs following inflammation triggered by the integrated actions of activated liver-resident macrophages (Kupffer cells) and hepatic stellate cells (HSCs), and the multiplicity of these mechanisms complicates drug therapy. Here, we demonstrate that the selective bromodomain and extra-terminal (BET) bromodomain inhibitor compound38 can block both the Janus kinase-signal transducer and activator of transcription and mitogen-activated protein kinase signaling pathways in macrophages, which decreased their secretion of proinflammatory cytokines in a dose-dependent manner. The inactivation of macrophages attenuated lipopolysaccharide-induced injurious inflammation concurrent with a reduction in F4/80+ cells, proinflammatory cytokine levels, and neutrophil infiltration. Moreover, compound 38 inhibited the Wnt/beta-catenin and transforming growth factor-beta/SMAD signaling pathways to abolish the activation of HSCs. In vivo, compound 38 significantly decreased the collagen deposition and fibrotic area of a CCl4-induced liver fibrosis model, and restored the deficiency of activated HSCs and the upregulation of liver inflammation. These results highlight the potential role of compound 38 in treating liver fibrosis considering its simultaneous inhibitory effects on liver inflammation and related fibrosis.
WOS关键词MOLECULAR-BASIS ; INJURY ; BRD4 ; RECOGNITION ; HOMEOSTASIS ; ACTIVATION ; MECHANISMS ; PROTEINS ; PACKAGE ; MATRIX
资助项目National Natural Science Foundation of China[82170617]
WOS研究方向Biotechnology & Applied Microbiology
语种英语
出版者TAYLOR & FRANCIS INC
WOS记录号WOS:000789278700001
源URL[http://119.78.100.183/handle/2S10ELR8/299283]  
专题新药研究国家重点实验室
通讯作者Li, Guang-Ming
作者单位1.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gastroenterol, Shanghai 200092, Yangpu District, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Zuchongzhi Dist, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Chinese Acad Sci, Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Zhejiang, Peoples R China
5.Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Res Ctr, Shanghai, Zhouyuan Distri, Peoples R China
推荐引用方式
GB/T 7714		 Fu, Rong,Zu, Shi-Jia,Liu, Yan-Jun,et al. Selective bromodomain and extra-terminal bromodomain inhibitor inactivates macrophages and hepatic stellate cells to inhibit liver inflammation and fibrosis[J]. BIOENGINEERED,2022,13(4):10914-10930.
APA Fu, Rong.,Zu, Shi-Jia.,Liu, Yan-Jun.,Li, Jia-Cheng.,Dang, Wen-Zhen.,...&Li, Guang-Ming.(2022).Selective bromodomain and extra-terminal bromodomain inhibitor inactivates macrophages and hepatic stellate cells to inhibit liver inflammation and fibrosis.BIOENGINEERED,13(4),10914-10930.
MLA Fu, Rong,et al."Selective bromodomain and extra-terminal bromodomain inhibitor inactivates macrophages and hepatic stellate cells to inhibit liver inflammation and fibrosis".BIOENGINEERED 13.4(2022):10914-10930.

入库方式： OAI收割

来源：上海药物研究所

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