Downregulation of Hepatic Stimulator Substance during the Early Phase of Liver Regeneration Inhibits E-cadherin Expression in Mice.

Downregulation of Hepatic Stimulator Substance during the Early Phase of Liver Regeneration Inhibits E-cadherin Expression in Mice. Int J Biochem Cell Biol. 2013 Dec 2; Authors: Zhang H, Dong LY, Sun G, An W Abstract Hepatic stimulatory substance (HSS), which encodes a sulfhydryl oxidase enzyme, promotes liver regeneration (LR) and maintains the viability of hepatocytes. Surprisingly, we found that the levels of the HSS mRNA and expressed protein were both strongly repressed at 12h after a 70% partial hepatectomy (PH) in mice. Understanding the mechanism and effect of this extraordinary suppression can provide a novel path for exploring the molecular function of HSS during LR. We observed that the EGF levels in the serum were negatively correlated with HSS expression in regenerating livers. Treating primary mouse hepatocytes or Hepa1-6 cells with EGF suppressed HSS mRNA expression. This suppression was transcriptional and was mediated by the effect of EGF on the phosphorylation of CCAAT/enhancer-binding protein β (C/EBPβ), which regulates HSS expression. We further showed that the enhanced phosphorylation of C/EBPβ after PH promoted its interaction with the HSS promoter and repressed HSS expression at early time-points after PH. Interestingly, the knockdown of HSS caused a dramatic decrease in E-cadherin expression in hepatocytes. E-cadherin expression was also significantly suppressed at 12h after PH. Moreover, the pre-injection of HSS-exp...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research