The Role Of C/Ebp-Alpha Expression In Human Liver And Liver Fibrosis And Its Relationship With Autophagy

Aim: To investigate the expression of CCAAT enhancer binding protein-alpha (C/EBP-alpha) in normal human liver and liver fibrosis and its probable association with autophagy. Methods: Double label immunohistochemistry was used to detect the location of C/EBP-alpha in hepatocytes and hepatic stellate cells (HSCs). The expression of C/EBP-alpha, Atg5, and Atg6 was also evaluated by immunohistochemistry in paraffin sections of human liver. HSC-T6 cells were treated with rapamycin and 3-methyladenine (3MA) to induce or inhibit autophagy, and the expression of C/EBP-alpha protein was detected by Western blotting. Results: Double label immunohistochemistry showed that C/EBP-alpha was predominantly located in hepatocytes and that its expression was significantly decreased in fibrosis compared with normal liver. Atg5 expression was increased in fibrosis but was located primarily in liver septa and peri-vascular areas, which was consistent with the distribution of HSCs. In contrast, Atg6 was not expressed in normal or fibrotic liver. Treatment of HSC-T6 cells in culture with rapamycin or 3MA decreased or increased C/EBP-x expression, respectively, as shown by Western blotting. Conclusion: C/EBP-alpha(was primarily expressed in hepatocytes in normal liver, but its expression decreased significantly in liver fibrosis. Autophagy might play a role in liver fibrosis through its association with C/EBP-alpha, but this hypothesis warrants further investigation.