Ibrahim, Ra and Dayoub, Rania and Melter, Michael and Weiss, Thomas S. (2018) Bile acids down-regulate the expression of Augmenter of Liver Regeneration (ALR) via SHP/HNF4 alpha 1 and independent of Egr-1. EXPERIMENTAL AND MOLECULAR PATHOLOGY, 105 (3). pp. 236-242. ISSN 0014-4800, 1096-0945
Full text not available from this repository. (Request a copy)Abstract
Bile acids (BA) are signaling molecules that activate nuclear factors and g-protein coupled receptors signaling to maintain metabolic homeostasis. However, accumulation of toxic BA promotes liver injury by initiating inflammation, inducing apoptosis and causing oxidative stress leading to cirrhosis and liver failure. Augmenter of Liver Regeneration (ALR) is a hepatotrophic growth factor with anti-apoptotic and anti-oxidative properties that has been shown to improve mitochondrial and hepatic functions in rats after bile duct ligation. In the current study we aimed to analyze the regulation of the pro-survival protein, ALR, under conditions of cytotoxic concentrations of BA. Promoter studies of ALR (- 733/ + 527 bp) revealed potential binding sites for various transcription factors like Egr-1, HNF4 alpha and two bile acid response elements (BARE). Using a full-length and several truncated promoter constructs for ALR we analyzed promoter activity and showed that BA reduce ALR promoter activity whereas Egr-1 transfection induces it. EMSA and supershift analysis confirmed the specific binding of Egr-1 to its response element within ALR promoter and this binding was reduced upon simultaneous stimulation with BA. We also showed that ALR promoter activity and protein expression are induced by HNF4 alpha 1 and repressed by SHP. In conclusion, these results indicate that BA negatively regulate ALR expression by SHP activation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR RECEPTOR; RESPONSE ELEMENT; ACTIVATION; PHOSPHORYLATION; IDENTIFICATION; CHOLESTASIS; HEPATOCYTES; MECHANISMS; APOPTOSIS; DNA; Augmenter of liver regeneration; Bile acids; Cholestasis; Early growth response protein-1; Small heterodimer partner |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Oct 2019 08:47 |
| Last Modified: | 04 Oct 2019 08:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13414 |
Actions (login required)
 |
View Item |
