首页|NF-κB/HDAC1/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis

NF-κB/HDAC1/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
  • 维普
The transcription factor nuclear factor kappa B (NF-κB) is activated in hepatocytes in the pathogenesis of hepatic steatosis.However,the action mechanism of NF-κB remains to be established in the hepatic steatosis.In this study,the P50 subunit of NF-κB was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes.The activity was supported by the phenotypes of P50 knockout (P50-KO) mice and P65 knockout (P65-KO) mice.Hepatic steatosis was reduced in the P50-KO mice,but not in the P65-KO mice.The reduction was a result of inhibition of HDAC1 activity in the P50-KO cells.Knockdown of Hdacl gene led to suppression of hepatocyte steatosis in HepG2 cells.A decrease in sterol-regulatory element binding protein 1c (SREBP1c) protein was observed in the liver of P50-KO mice and in cell with Hdac1 knockdown.The decrease was associated with an increase in succinylation of SREBP1c protein.The study suggests that P50 stabilizes HDAC1 to support the SREBP1c activity in hepatic steatosis in the pathophysiological condition.Interruption of this novel pathway in the P50-KO,but not the P65-KO mice,may account for the difference in hepatic phenotypes in the two lines of transgenic mice.

NF-κBHDAC1SREBP1SuccinylationHepatic steatosis

Yunwei Guo、Xiaoying Zhang、Zhiyun Zhao、Hongyun Lu、Bilun Ke、Xin Ye、Bin Wu、Jianping Ye

展开 >

Department of Gastroenterology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China

Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA

Shanghai Diabetes Institute, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China

National Key Research and Development Program of Chinastarting fund at Shanghai Jiao Tong University Affiliated Sixth People's Hospital to Jianping YeThe animal study was conduct

2018YFA0800603 to JY

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(5)
  • 4
  • 3