Identification of Nogo-B as a new molecular target of peroxisome proliferator-activated receptor gamma.

作者：Yu, Miao; Zhang, Shuang; Guo, Fangling; Yang, Xiaoxiao; Li, Qi; Wei, Zhuo; Han, Jihong; Duan, Yajun^*; Chen, Yuanli^*

来源：Cellular Signalling, 2019, 109429.

DOI：10.1016/j.cellsig.2019.109429

• Nogo-B
• PPARgamma
• fatty liver
• gene expression
• nuclear signaling
• rosiglitazone

Nonalcoholic fatty liver disease (NAFLD) is a fast-growing chronic liver disease worldwide which can lead to liver cirrhosis. Peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated transcription factor, plays an important role in lipogenesis. Increased Nogo-B expression can be determined in the liver of cirrhosis patients. However, the effect of PPARgamma activation on hepatic Nogo-B expression remains unknown. In this study, we found PPARgamma activation by rosiglitazone or dephosphorylation increased Nogo-B expression at mRNA and protein levels in HepG2 cells and mouse primary hepatocytes. Furthermore, we identified a PPARgamma response element (PPRE) in Nogo-B promoter and found PPARgamma enhanced Nogo-B transcription in a PPRE-dependent manner. ChIP assay further confirms rosiglitazone enhanced the binding of PPARgamma to Nogo-B promoter. Using a liver specific PPARgamma deficient mice, we determined the critical role of PPARgamma expression in regulating hepatic Nogo-B expression. Increased glucose and palmitate in culture medium activated Nogo-B and PPARgamma expression in mouse primary hepatocytes, and corresponding, high-fat diet (HFD) induced fatty liver associated with increased hepatic Nogo-B and PPARgamma expression in mice. Similarly, serum Nogo-B levels in patients with NAFLD were increased. However, rosiglitazone treatment reduced HFD-induced fatty liver and Nogo-B expression. In summary, our study identifies Nogo-B as a new molecular target of PPARgamma, and suggests increased Nogo-B might be a potential indicator for NAFLD.

• 单位
  合肥工业大学