Matrix-mediated changes in the expression of HNF-4alpha isoforms and in DNA-binding activity of ARP-1 in primary cultures of rat hepatocytes.

Autor: Runge D; Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA., Runge DM, Daskalakis N, Lubecki KA, Bowen WC, Michalopoulos GK
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1999 Jun 16; Vol. 259 (3), pp. 651-5.
DOI: 10.1006/bbrc.1999.0848
Abstrakt: Recently, we have developed a culture system in which rat hepatocytes dedifferentiate and proliferate and after the addition of EHS-gel redifferentiate. During both developmental stages HNF-4alpha2 mRNA was more abundant than HNF-4alpha1 mRNA. However, Western blot analysis using COS-7 cell-expressed HNF-4alpha1 and HNF-4alpha2 proteins as standards revealed that (i) HNF-4alpha2 protein was not expressed in dedifferentiated hepatocytes and (ii) either HNF-4alpha2 protein or a highly phosphorylated HNF-4alpha1 protein was the dominating isoform in redifferentiated hepatocytes. The changes in HNF4-isoform expression could not be mimicked by DMSO, suggesting them to be matrix specific. Furthermore, DMSO was less efficient than EHS-gel in reinducing liver-specific gene expression. EHS-gel overlay also led to reduction of ARP-1 DNA binding activity, while overall ARP-1 protein levels did not change. These results suggest that EHS-matrix overlay regulates the expression of different HNF-4alpha isoforms on a posttranscriptional level while ARP-1 DNA binding activity is regulated by posttranslational mechanisms.
(Copyright 1999 Academic Press.)
Databáze: MEDLINE
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