Protective Effect of 1,25-Dihydroxy Vitamin D3 on Pepsin–Trypsin-Resistant Gliadin-Induced Tight Junction Injuries
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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.
The aim of this study was to evaluate the effects of VD3 on PT–G-induced TJ injuries.
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.
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.
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.
KeywordsPepsin–trypsin-resistant gliadin 1,25-Dihydroxy vitamin D3 Tight junction MyD88 Zonulin release
SD performed the majority of the experiments. XW and HY performed the animal experiments and analyzed the data. HW and TPS designed the research. SD, TPS, and HW wrote the paper.
Compliance with ethical standards
Conflict of interest
All the authors declare that there are no conflict of interests for this article.
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