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Inhibition of protein arginine methyltransferase 1 alleviates liver fibrosis by attenuating the activation of hepatic stellate cells in mice

文献类型：期刊论文

作者Yan, Fang-Zhi3; Qian, Hui3; Liu, Fang3; Ding, Chen-Hong3; Liu, Shu-Qing3; Xiao, Meng-Chao2; Chen, Shi-Jie1; Zhang, Xin3; Luo, Cheng1; Xie, Wei-Fen3
刊名FASEB JOURNAL
出版日期2022-09-01
卷号36期号:9页码:14
关键词hepatic stellate cell inflammation inhibitor liver fibrosis protein arginine methyltransferase 1
ISSN号0892-6638
DOI10.1096/fj.202200238R
通讯作者Luo, Cheng(cluo@simm.ac.cn) ; Xie, Wei-Fen(weifenxie@medmail.com.cn)
英文摘要Protein arginine methyltransferase 1 (PRMT1) has been reported to be involved in various diseases. The expression of PRMT1 was increased in cirrhotic livers from human patients. However, the role of PRMT1 in hepatic fibrogenesis remains largely unexplored. In this study, we investigated the effect of PRMT1 on hepatic fibrogenesis and its underlying mechanism. We found that PRMT1 expression was significantly higher in fibrotic livers of the mice treated with thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Immunofluorescence staining revealed that PRMT1 expression was augmented in both hepatocytes and hepatic stellate cells (HSCs) in the fibrotic livers. Applying a selective inhibitor of PRMT1, PT1001B, significantly suppressed PRMT1 activity and mitigated liver fibrosis in mice. Hepatocyte-specific Prmt1 knockout did not affect liver fibrosis in mice. PRMT1 overexpression promoted the expression of fibrotic genes in the LX-2 cells, whereas knockdown of PRMT1 or treatment with PT1001B exhibited reversal effects, suggesting that PRMT1 plays an important role in HSC activation. Additionally, HSC-specific Prmt1 knockout attenuated HSC activation and liver fibrosis in TAA-induced fibrotic model. RNA-seq analysis revealed that Prmt1 knockout in HSCs significantly suppressed pro-inflammatory NF-kappa B and pro-fibrotic TGF-beta signals, and also downregulated the expression of pro-fibrotic mediators in mouse livers. Moreover, treatment with PT1001B consistently inhibited hepatic inflammatory response in fibrotic model. In conclusion, PRMT1 plays a vital role in HSC activation. Inhibition of PRMT1 mitigates hepatic fibrosis by attenuating HSC activation in mice. Therefore, targeting PRMT1 could be a feasible therapeutic strategy for liver fibrosis.
WOS关键词METHYLATION ; INFLAMMATION ; EXPRESSION ; MECHANISMS ; PRMT1
资助项目National Natural Science Foundation of China (NSFC)[82030021] ; National Natural Science Foundation of China (NSFC)[82072641] ; National Natural Science Foundation of China (NSFC)[81802324] ; National Natural Science Foundation of China (NSFC)[81870419]
WOS研究方向Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
语种英语
WOS记录号WOS:000839550800001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/302347]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Xie, Wei-Fen
作者单位1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Ctr Chem Biol,Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
2.Tongji Univ, Shanghai East Hosp, Dept Gastroenterol, Sch Med, Shanghai, Peoples R China
3.Naval Med Univ, Changzheng Hosp, Dept Gastroenterol, 415 Fengyang Rd, Shanghai 200003, Peoples R China
推荐引用方式
GB/T 7714		 Yan, Fang-Zhi,Qian, Hui,Liu, Fang,et al. Inhibition of protein arginine methyltransferase 1 alleviates liver fibrosis by attenuating the activation of hepatic stellate cells in mice[J]. FASEB JOURNAL,2022,36(9):14.
APA Yan, Fang-Zhi.,Qian, Hui.,Liu, Fang.,Ding, Chen-Hong.,Liu, Shu-Qing.,...&Xie, Wei-Fen.(2022).Inhibition of protein arginine methyltransferase 1 alleviates liver fibrosis by attenuating the activation of hepatic stellate cells in mice.FASEB JOURNAL,36(9),14.
MLA Yan, Fang-Zhi,et al."Inhibition of protein arginine methyltransferase 1 alleviates liver fibrosis by attenuating the activation of hepatic stellate cells in mice".FASEB JOURNAL 36.9(2022):14.

入库方式： OAI收割

来源：上海药物研究所

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