Biomol Ther.  2019 Feb;27(2):222-230. 10.4062/biomolther.2018.052.

Vitamin D Improves Intestinal Barrier Function in Cirrhosis Rats by Upregulating Heme Oxygenase-1 Expression

• Wang PF
• Yao DH
• Hu YY
• Li Y

• KMID: 2442015
• DOI: http://doi.org/10.4062/biomolther.2018.052

Abstract

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile CClâ‚„ (a mixture of pure CClâ‚„ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)â‚‚D₃(0.5 µg/100 g) and the vehicle were administered simultaneously with CClâ‚„ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in CClâ‚„-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.

Keyword

Bacterial translocation; Heme oxygenase-1; Vitamin D; Cirrhosis; Apoptosis; Proliferation

MeSH Terms

Animals
Apoptosis
Bacterial Translocation
Cholestasis
Enterocytes
Fibrosis*
Heme Oxygenase-1*
Heme*
Humans
Liver
Liver Diseases
Olive Oil
Oxidative Stress
Rats*
Tight Junctions
Vitamin D*
Vitamins*
Heme
Heme Oxygenase-1
Olive Oil
Vitamin D
Vitamins