Expression and regulation of liver regeneration associated protein ALR under patho-physiological conditions

摘要: Liver regeneration is a multistep and well-orchestrated process which initiated by injuries like tissue loss, infectious or toxic insults. It has been shown that expression of the hepatotrophic factor �Augmenter Regeneration� (ALR) increased within liver as well in diseases cirrhosis carcinoma. The aim this thesis was to analyze how ALR expressed, regulated what impact an altered might have on liver. Therefore, we investigated experimental models injury resemble hepatic patho-physiological disorders such fibrosis non-alcoholic steatohepatitis. mRNA could be upregulated independent different insults HCC tissues compared normal tissues. Furthermore, our results showed IL-6 rapidly induces protein level human hepatocytes hepatoma cells, whereas IL-1 beta reduces levels ALR. No changes observed after stimulation with growth factors suggesting only are known initiate regeneration. Further, analyzed promoter sequence identified putative regulatory elements for FOXA2, IL 6 RE BP C/EBP beta. Using luciferase assays EMSA, demonstrated both RE-BP not transactivate/bind promoter. In contrast, FOXA2 found regulate ALR, regulation amplified simultaneously activation using IL-6. Additionally, exhibits nearly conserved Nrf2 binding site underlining hepatoprotective function against oxidative stress. overexpressing HepG2 cells detect proliferation rate neither vitro nor vivo. ALR-overexpressing displayed enhanced acquirement adhere significant lower ability migrate invade wild type cells. adhesion molecule E-cadherin MMP-3 SNAIL explaining modulation conclusion, plays role its cause upstream cytokines. Addionally, it counteracts epithelial mesenchymal transition (EMT) application represents promising therapeutical strategy EMT involved.