Acute-phase response factor, increased binding, and target gene transcription during liver regeneration.
BACKGROUND & AIMS: The acute-phase response may contribute and influence cell-cycle progression in hepatocytes. The aim of this study was to examine the regulation of the alpha 2-macroglobulin gene during liver regeneration and molecular mechanisms that influence its expression. METHODS: Partial hepatectomy or sham surgery was performed in Sprague-Dawley rats. At different time points after surgery blood was taken from the liver vein, and nuclear extracts and RNA were prepared. Northern blot analysis, run-off assays, gel shift experiments, and cytokine assays were performed. RESULTS: Increased transcription of the alpha 2-macroglobulin gene was found 12-24 hours posthepatectomy and not after sham surgery. Increased levels of alpha 2-macroglobulin messenger RNA correlated with enhanced binding of acute-phase response factor/signal transducer and activator of transcription 3 (APRF/Stat3) towards the cognate DNA sequence in the alpha 2-macroglobulin promoter and dramatically increased interleukin-6 levels in the liver vein. In contrast, nuclear translocation of APRF/Stat3 was detected as early as 1 hour after hepatectomy and up to 48 hours posthepatectomy. Therefore, two events can be distinguished in the regulation of APRF/Stat3: Its nuclear translocation and increased DNA binding. CONCLUSIONS: Increased alpha 2-macroglobulin transcription posthepatectomy is achieved by increased levels of interleukin 6 and consecutive binding of APRF/Stat3 to the alpha 2-macroglobulin promoter. A two-step event is suggested for APRF/Stat3-dependent gene activation in hepatocytes.[1]References
- Acute-phase response factor, increased binding, and target gene transcription during liver regeneration. Trautwein, C., Rakemann, T., Niehof, M., Rose-John, S., Manns, M.P. Gastroenterology (1996) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
