Foxa2 (HNF-3 beta) regulates expression of hepatotrophic factor ALR in liver cells

Dayoub, Rania and Groitl, Peter and Dobner, Thomas and Bosserhoff, Anja Katrin and Schlitt, Hans-Juergen and Weiss, Thomas S. (2010) Foxa2 (HNF-3 beta) regulates expression of hepatotrophic factor ALR in liver cells. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 395 (4). pp. 465-470. ISSN 0006-291X, 1090-2104

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Abstract

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/EBP beta. 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/EBP beta 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. (C) 2010 Elsevier Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: MITOCHONDRIAL SULFHYDRYL OXIDASE; ENRICHED TRANSCRIPTION FACTORS; HEPATIC STIMULATOR SUBSTANCE; REGENERATION ALR; GENE-EXPRESSION; HUMAN HEPATOCYTES; GROWTH-FACTORS; AUGMENTOR; PROMOTER; YEAST; Augmenter of liver regeneration; GFER; Liver regeneration; Foxa2; HNF; IL-6
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Jul 2020 11:03
Last Modified: 30 Jul 2020 11:03
URI: https://pred.uni-regensburg.de/id/eprint/24731

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