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Gut. 2015 May;64(5):791-9. doi: 10.1136/gutjnl-2014-307024. Epub 2014 Aug 18.

Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently.

Author information

1
Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
2
The Institute of Hepatology, Regeneration and Repair Group, London, UK.
3
Institute for Pathology, University Hospital Cologne, Cologne, Germany.
4
Department of General, Visceral and Transplantation Surgery, University Hospital, University Duisburg-Essen, Essen, Germany.
5
Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany Rodos BioTarget GmbH, Medical Park Hannover, Hannover, Germany.

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.

KEYWORDS:

CELL SIGNALLING; GENETIC POLYMORPHISMS; HEPATIC FIBROSIS; HEPATIC STELLATE CELL; NONALCOHOLIC STEATOHEPATITIS

PMID:
25134788
DOI:
10.1136/gutjnl-2014-307024
[Indexed for MEDLINE]

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