Recently, emerging evidence shows that dysregulation of circadian genes is closely associated with liver fibrosis. However, how dysregulation of circadian genes promotes liver fibrosis is unknown. In this study, we show that neuronal PAS domain protein 2 (NPAS2), one of the core circadian molecules that has been shown to promote hepatocarcinoma cell proliferation, significantly contributed to liver fibrogenesis. NPAS2 is upregulated in hepatic stellate cells (HSCs) after fibrogenic injury, which subsequently contributes to the activation of HSCs. Mechanistically, NPAS2 plays a profibrotic role via direct transcriptional activation of hairy and enhancer of split 1 (Hes1), a critical transcriptor of Notch signaling for the fibrogenesis process, in HSCs. Our findings demonstrate that NPAS2 plays a critical role in liver fibrosis through direct transcriptional activation of Hes1, indicating that NPAS2 may serve as an important therapeutic target to reverse the progression of liver fibrosis.
基金：
National Natural Science Foundation
of China (grants 81600478, 81802345, 81772934) and by the State Key
Laboratory of Cancer Biology Project (CBSKL2017Z01)
第一作者机构：[1]Fourth Mil Med Univ, Tangdu Hosp, Dept Pain Treatment, 1 Xinsi Rd, Xian 710038, Shaanxi, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Fourth Mil Med Univ, Tangdu Hosp, Dept Pain Treatment, 1 Xinsi Rd, Xian 710038, Shaanxi, Peoples R China[7]Chongqing Med Univ, Affiliated Hosp 1, Dept Hematol, Chongqing 400016, Peoples R China[8]Xian Cent Hosp, Dept Hematol, Xian 710003, Shaanxi, Peoples R China[9]Shaanxi Prov Peoples Hosp, Dept Hepatobiliary Surg, 256 West Friendship Rd, Xian 710068, Shaanxi, Peoples R China[*1]Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, 256 West Friendship Road, Xi’an 710068, China[*2]Department of Pain Treatment, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi’an 710038, China[*3]Department of Hematology, Xi’an Central Hospital, Xi’an, Shaanxi 710003, China.
推荐引用方式(GB/T 7714)：
Yang Tao,Yuan Peng,Yang Yi,et al.NPAS2 Contributes to Liver Fibrosis by Direct Transcriptional Activation of Hes1 in Hepatic Stellate Cells[J].MOLECULAR THERAPY-NUCLEIC ACIDS.2019,18:1009-1022.doi:10.1016/j.omtn.2019.10.025.
APA：
Yang, Tao,Yuan, Peng,Yang, Yi,Liang, Ning,Wang, Qian...&Chang, Hulin.(2019).NPAS2 Contributes to Liver Fibrosis by Direct Transcriptional Activation of Hes1 in Hepatic Stellate Cells.MOLECULAR THERAPY-NUCLEIC ACIDS,18,
MLA：
Yang, Tao,et al."NPAS2 Contributes to Liver Fibrosis by Direct Transcriptional Activation of Hes1 in Hepatic Stellate Cells".MOLECULAR THERAPY-NUCLEIC ACIDS 18.(2019):1009-1022
医学