Abstract
Background
The toll-like receptor 4 (TLR4) has been reported to play an important role in necrotizing enterocolitis (NEC). As an established regulator of TLR4, vitamin D has been demonstrated to be intestinal-protective. This study aims at finding out whether the vitamin D/vitamin D receptor (VDR) pathway ameliorates NEC by regulating TLR4.
Methods
Serum 25-hydrovitamin D (25(OH)D) was tested and compared in 15 preterm infants with NEC, 12 preterm infants without known complications and 20 healthy term infants. Neonatal Wistar rats were grouped and NEC was induced through formula feeding and cold/asphyxia stress. Vitamin D and the vehicle were administered to compare the microscopic structure, apoptotic protein expression, intestinal barrier function, inflammatory response, and TLR4 expression.
Results
Preterm infants with NEC had significantly lower 25(OH)D levels than those without NEC and healthy subjects. VDR expression was suppressed, whereas TLR4 expression was elevated in the NEC intestine. Vitamin D may increase the survival rate, alleviate structure damage, and preserve intestinal barrier function. These were achieved partly through restoration of VDR and suppression of TLR4.
Conclusion
NEC infants have lower levels of vitamin D. The vitamin D/VDR pathway protects against intestinal injury of NEC partly through suppressing the expression of TLR4.
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Acknowledgements
This study was supported by the National Nature Science Foundation of China (81700459, 81571479, and 81471489).
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Shi, Y., Liu, T., Zhao, X. et al. Vitamin D ameliorates neonatal necrotizing enterocolitis via suppressing TLR4 in a murine model. Pediatr Res 83, 1024–1030 (2018). https://doi.org/10.1038/pr.2017.329
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DOI: https://doi.org/10.1038/pr.2017.329
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