Abstract
BackgroundTight 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 D3 affects intestinal mucosal barrier stability via the Notch signaling pathway.MethodsIntestinal 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 VD3 + 100 mg/kg d VC), low VC group (LVC, 200 IU/kg d VD3 + 10 mg/kg d VC), medium VC group (MVC, 200 IU/kg d VD3 + 100 mg/kg d VC), and high VC group (HVC, 200 IU/kg d VD3 + 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); VD3 group (0.1 μmol/L VD3); VC + VD3 group (0.1, 1, 5, 10 μmol/mL VC + 0.1 μmol/L VD3).ResultsElectron microscopy analysis revealed that both low and high doses of vitamin C combined with vitamin D3 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 D3 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 D3 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.ConclusionsWe found that vitamin C combined with vitamin D3 protected against dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal mucosa.
Highlights
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes irritation, inflammation, and ulcers in the lining of the large intestine or colon
We evaluated vitamin C combined with vitamin D3 in in vitro and in vivo intervention experiments in a UC model to explore whether combining these vitamins has greater protective effects on the intestinal mucosal barrier and to explore the role of the Notch signaling pathway in the intestinal mucosal barrier
We found that in the high-dose vitamin C (VC) group, the mRNA expression level of signal molecules in the Notch/ Hes-1 pathway was significantly decreased, the expression level of the tight junction protein zona occludens (ZO)-1 mRNA was increased; ZO-1 interacts with claudin-2 to correct the increase in permeability caused by disease [31], and highdose VC significantly improved colonic tissue shortening caused by dextran sodium sulfate (DSS) in guinea pigs
Summary
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes irritation, inflammation, and ulcers in the lining of the large intestine or colon. As an important interface between the body and external environment, the intestinal mucosal barrier plays a key role in maintaining intestinal homeostasis. Many studies have shown that intestinal mucosal damage is the initiating factor of IBD. Protecting and repairing the intestinal mucosal barrier is key to preventing the development of IBD. Tight junction proteins play crucial roles in maintaining the intestinal mucosal barrier. 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
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