Vitamin D modulates biliary fibrosis in ABCB4-deficient mice |
| |
Authors: | Katrin Hochrath Caroline S Stokes Jürgen Geisel Marion J Pollheimer Peter Fickert Steven Dooley Frank Lammert |
| |
Institution: | 1. Department of Medicine II, Saarland University Medical Center, Kirrberger Str. 100, 66421, Homburg, Germany 2. Institute of Clinical Chemistry and Laboratory Medicine, Saarland University Medical Center, Homburg, Germany 3. Insititute of Pathology, Medical University Graz, Graz, Austria 4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 5. Division of Molecular Hepatology-Alcohol Associated Diseases, Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
|
| |
Abstract: | Purpose Impaired vitamin D receptor signaling represents an aggravating factor during liver injury, and recent studies suggest that vitamin D might exert a protective role in chronic hepatobiliary diseases. We hypothesized that vitamin D supplementation would ameliorate liver fibrosis in ATP-binding cassette transporter B4 knockout (Abcb4 ?/?) mice as a preclinical model of sclerosing cholangitis. Methods Abcb4 ?/? and wild-type mice were fed a regular chow diet (600 IU vitamin D/kg food) or diets with lower (100 IU/kg) and higher (2,400 IU/kg) vitamin D concentrations for 12 weeks. Serum 25-hydroxyvitamin D concentrations were measured by chemiluminescence immunoassays. Liver injury and biliary fibrosis were assessed by liver enzyme activities, histopathology and hepatic collagen contents. Hepatic mRNA expression of markers for fibrosis, vitamin D and bile acid metabolism were analyzed by quantitative PCR. Results Different vitamin D concentrations were observed depending on genotype and diet group, with Abcb4 ?/? mice on the control diet showing lower vitamin D concentrations compared to wild-type mice. Abcb4 ?/? animals on the low vitamin D diet demonstrated the most advanced liver fibrosis and highest hepatic collagen contents. Feeding Abcb4 ?/? mice a high vitamin D diet enriched serum vitamin D levels, lowered liver enzyme activities, altered expression levels of profibrogenic genes and ameliorated, in part, liver injury. Conclusions This is the first report to demonstrate that fibrogenesis in the established Abcb4 ?/? model is influenced by vitamin D supplementation. Since vitamin D modulates sclerosing cholangitis in vivo, we speculate that sufficient vitamin D intake might improve liver damage and induce antifibrotic effects in chronic cholestasis in humans. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|