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The Active Constituent From Gynostemma Pentaphyllum Prevents Liver Fibrosis Through Regulation of the TGF-beta 1/NDRG2/MAPK Axis
Huang, Hui2,4,5; Wang, Kuifeng1,3; Liu, Qian2,4,5; Ji, Feihong1,3; Zhou, Hu2,4,5; Fang, Shanhua2,4; Zhu, Jiansheng1
刊名FRONTIERS IN GENETICS
2020-11-04
卷号11页码:11
关键词HSC TGF-β 1 liver fibrosis quantitative proteomics NDRG2
DOI10.3389/fgene.2020.594824
通讯作者Fang, Shanhua(shanhua125@163.com) ; Zhu, Jiansheng(zhujs@enzemed.com)
英文摘要Liver fibrosis resulting from chronic liver damage constitutes a major health care burden worldwide; however, no antifibrogenic agents are currently available. Our previous study reported that the small molecule NPLC0393 extracted from the herb Gynostemma pentaphyllum exerts efficient antifibrotic effects both in vivo and in vitro. In this study, a TMT-based quantitative proteomic study using a carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was performed to identify the potential target of NPLC0393. Combining this study with bioinformatic analysis of differentially expressed proteins between the CCl4 model and NPLC0393 treatment groups, we focused on the function of N-myc downstream-regulated gene 2 (NDRG2) involved in cell differentiation. In vitro studies showed that NPLC0393 prevented the TGF-beta 1 stimulation-induced decrease in the NDRG2 level in hepatic stellate cells (HSCs). Functional studies indicated that NDRG2 can inhibit the activation of HSCs by preventing the phosphorylation of ERK and JNK. Furthermore, knockdown of NDRG2 abolished the ability of NPLC0393 to inhibit HSC activation. In conclusion, these results provide information on the mechanism underlying the antifibrotic effect of NPLC0393 and shed new light on the potential therapeutic function of the TGF-beta 1/NDRG2/MAPK signaling axis in liver fibrosis.
资助项目National Key Research and Development Program from the Ministry of Science and Technology of China[2017YFC1700200] ; National Natural Science Foundation of China[81500469] ; Science and Technology Plan of Taizhou City, Zhejiang Province[131ky13] ; Zhejiang Provincial Natural Science Foundation of China[Y15H030004]
WOS关键词R-PACKAGE ; NDRG2 ; BETA ; GENE ; PROLIFERATION ; CELLS
WOS研究方向Genetics & Heredity
语种英语
出版者FRONTIERS MEDIA SA
WOS记录号WOS:000591495000001
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/292638]  
专题中国科学院上海药物研究所
通讯作者Fang, Shanhua; Zhu, Jiansheng
作者单位1.Wenzhou Med Univ, Affiliated Taizhou Hosp, Dept Infect Dis, Taizhou, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai, Peoples R China
3.Suzhou GenHouse Pharmaceut Co Ltd, Suzhou, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
5.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Huang, Hui,Wang, Kuifeng,Liu, Qian,et al. The Active Constituent From Gynostemma Pentaphyllum Prevents Liver Fibrosis Through Regulation of the TGF-beta 1/NDRG2/MAPK Axis[J]. FRONTIERS IN GENETICS,2020,11:11.
APA Huang, Hui.,Wang, Kuifeng.,Liu, Qian.,Ji, Feihong.,Zhou, Hu.,...&Zhu, Jiansheng.(2020).The Active Constituent From Gynostemma Pentaphyllum Prevents Liver Fibrosis Through Regulation of the TGF-beta 1/NDRG2/MAPK Axis.FRONTIERS IN GENETICS,11,11.
MLA Huang, Hui,et al."The Active Constituent From Gynostemma Pentaphyllum Prevents Liver Fibrosis Through Regulation of the TGF-beta 1/NDRG2/MAPK Axis".FRONTIERS IN GENETICS 11(2020):11.
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