Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats

Abramovitch, Shirley; Dahan-Bachar, L; Sharvit, Efrat; Weisman, Yosef; A, Ben Tov; Brazowski, Eli; Reif, Shimon

doi:10.1136/gut.2010.234666

Cited by 252 publications

(217 citation statements)

References 37 publications

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“…After activation, HSCs transform from quiescent vitamin A-storing cells to myofibroblast-like cells and accumulate ECM proteins, mostly type 1 collagen. Interestingly, there is in vitro evidence that VD administration may inhibit HSC activation by different pro-fibrogenic pathways (26,32). The recent findings that phototherapy improves liver histology (33) and that VD supplementation prevents liver fibrosis (26) in animal models of NAFLD support a potential role of VD in the prevention and treatment of NASH.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease

Nobili

Giorgio

Liccardo

et al. 2014

European Journal of Endocrinology

103

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Objective: To investigate the association between plasma vitamin D (VD) levels and histological liver damage in children with nonalcoholic fatty liver disease (NAFLD). Subjects and methods: In this cross-sectional study, carried out in a tertiary care center for obesity, 73 consecutive overweight and obese children with persistently elevated serum aminotransferase levels and diffusely hyperechogenic liver on ultrasonography were selected for liver biopsy. Nonalcoholic steatohepatitis (NASH) and fibrosis were histologically diagnosed using NAFLD Clinical Research Network (CRN) criteria. The plasma levels of 25-OH-VD were measured by HPLC. Bone mineral density (BMD) of lumbar spine was evaluated by dual-energy X-ray absorptiometry. Multiple linear regression analysis was used to evaluate the association between 25-OH-VD levels and the predictors of interest after correction for age, gender, waist circumference, BMI, and other potential confounders. Results: The children (64% males) were aged 8-18 years, and their median BMI was 2.45 SDS. Both parathyroid hormone levels and BMD were within the normal range. All cases of fibrosis were detected in children with NASH. On multivariable linear regression with correction for age, gender, and BMI, 25-OH-VD levels were found to be 9 (95% CI 12-6) ng/ml lower in children with NASH than in those without NASH (P!0.001) and 9 (12-6) ng/ml lower in children with stage 1 fibrosis than in those with stage 0 fibrosis and 9 (13-6) ng/ml lower in children with stage 2 than in those with stage 0 fibrosis (P!0.001 for both). Conclusion: VD levels are inversely associated with NASH and fibrosis in children with NAFLD.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, both animal and human data suggest that 1,25(OH) 2 VD may have anti-fibrogenic effects (25,26). Selected VDR polymorphisms have been reported to be associated with primary biliary cirrhosis (27).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease

Nobili

Giorgio

Liccardo

et al. 2014

European Journal of Endocrinology

103

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“…The vitamin D receptor (VDR) is activated by secondary bile acids such as lithocholic acid (Makishima et al, 2002). The impact of VDR activation on bile acid metabolism and cholestatic disease is difficult to predict, because it inhibited FXR-dependent gene transactivation in vitro, but also had antifibrotic effects in a rat model of liver fibrosis Abramovitch et al, 2011). VDR does not seem to have a significant impact on the expression of canalicular ABC transporters.…”

Section: Bile Acid Metabolism and Its Regulationmentioning

confidence: 99%

The Role of Canalicular ABC Transporters in Cholestasis

et al. 2014

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Cholestasis, a hallmark feature of hepatobiliary disease, is characterized by the retention of biliary constituents. Some of these constituents, such as bile acids, inflict damage to hepatocytes and bile duct cells. This damage may lead to inflammation, fibrosis, cirrhosis, and eventually carcinogenesis, sequelae that aggravate the underlying disease and deteriorate clinical outcome. Canalicular ATP-binding cassette (ABC) transporters, which mediate the excretion of individual bile constituents, play a key role in bile formation and cholestasis. The study of these transporters and their regulatory nuclear receptors has revolutionized our understanding of cholestatic disease. This knowledge has served as a template to develop novel treatment strategies, some of which are currently already undergoing phase III clinical trials. In this review we aim to provide an overview of the structure, function, and regulation of canalicular ABC transporters. In addition, we will focus on the role of these transporters in the pathogenesis and treatment of cholestatic bile duct and liver diseases.

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“…Of course, there are some common mechanisms in the action of vitamin D that may benefit both autoimmune and viral disorders. For example, the antiproliferative and antifibrotic effects of 1,25(OH) 2 D on liver fibrosis found in in vitro and in vivo models (Abramovitch et al, 2011) may be considered as having a potential role in the mechanisms of beneficial effect of vitamin D on liver diseases related to both autoimmune and viral infections. Furthermore, it is unclear whether there are the U-shaped exposure-risk relationships between vitamin D concentrations and disease outcomes in the autoimmune and viral diseases, as have been proposed in prostate cancer (Tuohimaa et al, 2004), with both low and high concentrations, in comparison with the middle-range concentration, of vitamin D being associated with disease outcomes.…”

Section: Discussionmentioning

confidence: 99%

Single-Nucleotide Polymorphism at CYP27B1-1260, but Not VDR Taq I, Is Possibly Associated with Persistent Hepatitis B Virus Infection

Zhu

Li²,

Han³

et al. 2012

Genetic Testing and Molecular Biomarkers

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Background: Vitamin D, beyond its role in calcium and bone metabolism, exhibits immunomodulatory effects on innate and adaptive immune pathways and is suggestively related to liver diseases. Objective: This study investigated the association of single-nucleotide polymorphisms in genes involved in vitamin D functions with hepatitis B virus (HBV) infection. Methods: Five hundred Chinese Han subjects, including 274 chronic HBV patients, 68 HBV infection resolvers, and 158 healthy controls without HBV infection, were studied. The CYP27B1-1260 promoter and the VDR Taq I polymorphisms were genotyped by polymerase chain reactionrestriction fragment length polymorphism. Results: Although there was no difference between HBV patients and healthy controls, HBV patients and healthy controls had a higher frequency of the CYP27B1-1260 genotype CC (15.0% vs. 2.9%, p = 0.004 and 13.3% vs. 2.9%, p = 0.006, respectively) and allele C (38.3% vs. 25.7%, p = 0.006 and 39.2% vs. 25.7%, p = 0.006, respectively) compared with resolvers. The genotype and allele frequencies of the VDR Taq I polymorphism had no difference between patients, resolvers, and healthy controls. Conclusion: These results suggest that the CYP27B1-1260 promoter polymorphism is possibly associated with the persistence, but not susceptibility to HBV infection in Chinese HBV patients, and that the VDR Taq I polymorphism is not suggested to be related to chronic HBV infection.

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Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats

Abstract: 1,25(OH)(2)D(3) has antiproliferative and antifibrotic effects on liver fibrosis in in vitro and in vivo models and may be considered as having potential therapeutic value.

Cited by 252 publications

References 37 publications

Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease

Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease

The Role of Canalicular ABC Transporters in Cholestasis

Single-Nucleotide Polymorphism at CYP27B1-1260, but Not VDR Taq I, Is Possibly Associated with Persistent Hepatitis B Virus Infection

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