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Dig Dis Sci. 2018 Jan;63(1):92-104. doi: 10.1007/s10620-017-4738-0. Epub 2017 Sep 4.

Protective Effect of 1,25-Dihydroxy Vitamin D3 on Pepsin-Trypsin-Resistant Gliadin-Induced Tight Junction Injuries.

Dong S1,2, Singh TP1,2, Wei X1,2, Yao H1,2, Wang H3,4.

Author information

1
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
2
The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, Hubei, China.
3
Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. zhnwhl@whu.edu.cn.
4
The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, Hubei, China. zhnwhl@whu.edu.cn.

Abstract

BACKGROUND:

Tight junction (TJ) injuries induced by pepsin-trypsin-resistant gliadin (PT-G) play an important role in the pathogenesis of celiac disease. Previously, 1,25-dihydroxy vitamin D3 (VD3) was reported to be a TJ regulator that attenuates lipopolysaccharide- and alcohol-induced TJ injuries. However, whether VD3 can attenuate PT-G-induced TJ injuries is unknown.

AIM:

The aim of this study was to evaluate the effects of VD3 on PT-G-induced TJ injuries.

METHODS:

Caco-2 monolayers were used as in vitro models. After being cultured for 21 days, the monolayers were treated with PT-G plus different concentrations of VD3. Then, the changes in trans-epithelial electrical resistance and FITC-dextran 4000 (FD-4) flux were determined to evaluate the monolayer barrier function. TJ protein levels were measured to assess TJ injury severity, and myeloid differentiation factor 88 (MyD88) expression and zonulin release levels were determined to estimate zonulin release signaling pathway activity. Additionally, a gluten-sensitized mouse model was established as an in vivo model. After the mice were treated with VD3 for 7 days, we measured serum FD-4 concentrations, TJ protein levels, MyD88 expression, and zonulin release levels to confirm the effect of VD3.

RESULTS:

Both in vitro and in vivo, VD3 significantly attenuated the TJ injury-related increase in intestinal mucosa barrier permeability. Moreover, VD3 treatment up-regulated TJ protein expression levels and significantly decreased MyD88 expression and zonulin release levels.

CONCLUSIONS:

VD3 has protective effects against PT-G-induced TJ injuries both in vitro and in vivo, which may correlate with the disturbance of the MyD88-dependent zonulin release signaling pathway.

KEYWORDS:

1,25-Dihydroxy vitamin D3; MyD88; Pepsin–trypsin-resistant gliadin; Tight junction; Zonulin release

PMID:
28871457
DOI:
10.1007/s10620-017-4738-0
[Indexed for MEDLINE]

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