Combined effect of vitamin C and vitamin D(3) on intestinal epithelial barrier by regulating Notch signaling pathway

BACKGROUND: Tight junction proteins play crucial roles in maintaining the intestinal mucosal barrier. Although previous studies have shown that Notch signaling is closely related to tight junction proteins, the mechanism remains unclear. This study was performed to investigate whether vitamin C combined with vitamin D(3) affects intestinal mucosal barrier stability via the Notch signaling pathway. METHODS: Intestinal epithelial barrier and notch signaling pathway were studied using guinea pig and SW480 cells. The guinea pigs were randomized into four groups (n = 6 in each group): control group (C, 200 IU/kg d VD(3) + 100 mg/kg d VC), low VC group (LVC, 200 IU/kg d VD(3) + 10 mg/kg d VC), medium VC group (MVC, 200 IU/kg d VD(3) + 100 mg/kg d VC), and high VC group (HVC, 200 IU/kg d VD(3) + 200 mg/kg d VC). Except for the control group, the other three groups were freely drinked with 2% dextran sodium sulfate solution for 4 days. And the control group was free to drink distilled water. The following cell groups were used: control group (SW480 cells without intervention); LPS group (100 ng/mL LPS); VD(3) group (0.1 μmol/L VD(3)); VC + VD(3) group (0.1, 1, 5, 10 μmol/mL VC + 0.1 μmol/L VD(3)). RESULTS: Electron microscopy analysis revealed that both low and high doses of vitamin C combined with vitamin D(3) maintained dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal epithelium tight junction. Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of the high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, cell migration and repair following treatment with different concentrations of vitamin C combined with vitamin D(3) were significantly improved and the protein expression of Notch-1 was increased, whereas the protein expression of claudin-2 was significantly decreased. Thus, our results demonstrate that an appropriate amount of vitamin C combined with vitamin D(3) can regulate the expression of claudin-2 by regulating Notch-1, relieve destruction of the intestinal mucosal barrier, and promote the repair of damage to the cell mucosal barrier. CONCLUSIONS: We found that vitamin C combined with vitamin D(3) protected against dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal mucosa.