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

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....

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Bibliographic Details
Published in:Digestive diseases and sciences 2018-01, Vol.63 (1), p.92-104
Main Authors: Dong, Shouquan, Singh, Tikka Prabhjot, Wei, Xin, Yao, Huang, Wang, Hongling
Format: Article
Language:English
Subjects:
Analysis
Biochemistry
Dextran
Gastroenterology
Gluten
Hepatology
Injuries
Kinases
Medicine
Medicine & Public Health
Oncology
Original Article
Permeability
Proteins
Rodents
Transplant Surgery
Trypsin
Vitamins
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Summary: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.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-017-4738-0