Biomol Ther  
Vitamin D Improves Intestinal Barrier Function in Cirrhosis Rats by Upregulating Heme Oxygenase-1 Expression
Peng-fei Wang1,†, Dan-hua Yao1,†, Yue-yu Hu2 and Yousheng Li1,*
1Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011,
2Department of Neurology, The Fourth Affiliated Hospital of Tongji University, Shanghai 200081, China
E-mail: lyswpf@gmail.com
Tel: +86-18019790260, Fax: +86-21-63136856.
The first two authors contributed equally to this work.
Received: March 21, 2018; Revised: June 4, 2018; Accepted: July 17, 2018; Published online: September 3, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

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 CCl4 (a mixture of pure CCl4 and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)2D3 (0.5 ug/100 g) and the vehicle were administered simultaneously with CCl4 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 CCl4-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.
Keywords: Bacterial translocation, Heme oxygenase-1, Vitamin D, Cirrhosis, Apoptosis, Proliferation


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