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Gut doi:10.1136/gutjnl-2014-307024
Hepatology
Original article
Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently
Anja Beilfuss1,
Jan-Peter Sowa1,
Svenja Sydor1,
Mechthild Beste1,
Lars P Bechmann1,
Martin Schlattjan1,
Wing-Kin Syn2,
Inga Wedemeyer3,
Zoltan Mathé4,
Christoph Jochum1,
Guido Gerken1,
Robert K Gieseler1,5,
Ali Canbay1
+ Author Affiliations
1Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
2The Institute of Hepatology, Regeneration and Repair Group, London, UK
3Institute for Pathology, University Hospital Cologne, Cologne, Germany
4Department of General, Visceral and Transplantation Surgery, University Hospital, University Duisburg-Essen, Essen, Germany
5Rodos BioTarget GmbH, Medical Park Hannover, Hannover, Germany
Correspondence to Professor Ali Canbay, Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany; [email protected]
Received 14 February 2014
Accepted 31 July 2014
Published Online First 18 August 2014
Abstract
Objective 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.
Design 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.
Results 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.
Conclusions 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.
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发表于 2014-8-21 11:26
