Foxa2 (HNF-3beta) regulates expression of hepatotrophic factor ALR in liver cells.
Liver regeneration is a multistep and well-orchestrated process which is initiated by injuries such as tissue loss, infectious or toxic insults. Augmenter of liver regeneration (ALR) is a hepatotrophic growth factor which has been shown to stimulate hepatic regeneration after partial hepatectomy and therefore seems to be regulated during the regenerative process in the liver. Our aim was to analyze how ALR is regulated in hepatic tissues and which transcription factors might regulate its tissue-specific expression. Promoter studies of ALR (-733/+527 bp) revealed potential regulatory elements for various transcription factors like Foxa2, IL-6 RE-BP and C/EBPbeta. Analysis of the promoter activity by performing luciferase assays revealed that co-transfection with Foxa2 significantly induced the activity of ALR promoter in HepG2 cells. EMSA and Supershift analysis using anti-Foxa2 antibody confirmed the specific binding of Foxa2 to ALR promoter and this binding was inducible when the cells were simultaneously stimulated with IL-6. The increased binding after activation with IL-6 and/or Foxa2 was confirmed by elevated ALR protein levels using Western blot technique. In addition, we could not detect any binding of C/EBPbeta and IL-6 RE-BP to the promoter of ALR. In conclusion, these results indicate that ALR is regulated by Foxa2, and this regulation may be amplified by IL-6.
Dayoub
Rania
R
Center for Liver Cell Research, University Medical Center Regensburg, Germany.
Groitl
Peter
P
Dobner
Thomas
T
Bosserhoff
Anja Katrin
AK
Schlitt
Hans-Jürgen
HJ
Weiss
Thomas S
TS
D001483:Base Sequence; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007438:Introns; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008115:Liver Regeneration / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D050862:Oxidoreductases Acting on Sulfur Group Donors
D022782:CCAAT-Enhancer-Binding Protein-beta; D051542:Hepatocyte Nuclear Factor 3-beta; D015850:Interleukin-6; D011506:Proteins; C545012:CEBPB protein, human; C496502:FOXA2 protein, human; C088825:GFER protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors