Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Beilfuss, A; Sowa, JP; Sydor, S; Beste, M; Bechmann, LP; Schlattjan, M; Syn, WK; Wedemeyer, I; Mathé, Z; Jochum, C; Gerken, G; Gieseler, RK; Canbay, A.
Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently.
Gut. 2015; 64(5):791-799
Doi: 10.1136/gutjnl-2014-307024
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Mathe Zoltan
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- Abstract:
- Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity and constitutes part of the metabolic syndrome, which have been associated with low serum vitamin D (VD). Due to known crosstalk between VD and transforming growth factor (TGF)-β signalling, VD has been proposed as an antifibrotic treatment. We evaluated the association between VD, the vitamin D receptor (VDR) and liver fibrosis in primary human hepatic stellate cells (phHSC) and 106 morbidly obese patients with NAFLD. Treating phHSC with VD ameliorated TGF-β-induced fibrogenesis via both VDR-dependent and VDR-independent mechanisms. Reduction of fibrogenic response was abolished in cells homozygous for GG at the A1012G single nucleotide polymorphisms within the VDR gene. Compared with healthy livers, NAFLD livers expressed higher levels of VDR mRNA and VDR fragments. VDR mRNA was lower in patients homozygous for GG at A1012G and expression of pro-fibrogenic genes was higher in patients carrying the G allele. VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Cells, Cultured -
- Drug Evaluation, Preclinical - methods
- Female -
- Gene Expression Regulation - physiology
- Gene Knockdown Techniques - methods
- Hepatic Stellate Cells - drug effects
- Hepatic Stellate Cells - physiology
- Humans -
- Liver - metabolism
- Liver Cirrhosis - genetics
- Liver Cirrhosis - metabolism
- Male -
- Middle Aged -
- Non-alcoholic Fatty Liver Disease - etiology
- Non-alcoholic Fatty Liver Disease - genetics
- Non-alcoholic Fatty Liver Disease - metabolism
- Non-alcoholic Fatty Liver Disease - pathology
- Obesity, Morbid - complications
- Obesity, Morbid - metabolism
- Polymorphism, Single Nucleotide -
- RNA, Messenger - genetics
- Receptors, Calcitriol - genetics
- Receptors, Calcitriol - metabolism
- Receptors, Calcitriol - physiology
- Signal Transduction - physiology
- Smad2 Protein - metabolism
- Transforming Growth Factor beta - antagonists & inhibitors
- Transforming Growth Factor beta - pharmacology
- Transforming Growth Factor beta - physiology
- Vitamin D - blood
- Vitamin D - pharmacology
- Young Adult -