Vitamin D protects against necrotising enterocolitis in newborn mice by activating the ERK signalling pathway

Lyu,Chunmei; Jiang,Suhua; Kong,Muxian; Chen,Xiaoqian; Zhang,Li

doi:10.3892/mmr.2020.11286

Vitamin D protects against necrotising enterocolitis in newborn mice by activating the ERK signalling pathway

Authors:
- Chunmei Lyu
- Suhua Jiang
- Muxian Kong
- Xiaoqian Chen
- Li Zhang
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Affiliations: Department of Pediatrics, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China, Department of Nursing, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China
Published online on: June 26, 2020 https://doi.org/10.3892/mmr.2020.11286
Pages: 2107-2114

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Abstract

Necrotising enterocolitis (NEC) is a serious intestinal disease that occurs in the neonatal period. The present study aimed to investigate the protective effect of vitamin D on NEC and the underlying mechanisms. Artificial feeding and hypoxia‑cold stimulation were used to establish a mouse NEC model. IEC‑6 cells were treated with lipopolysaccharide (LPS) to establish the in vitro NEC model. Changes in the levels of interleukin (IL)‑6, IL‑1β and tumour necrosis factor (TNF)‑α, and activities of malondialdehyde (MDA) and glutathione peroxidase (GPx) were investigated via ELISA kits. In addition, mRNA expression of IL‑6, IL‑1β and TNF‑α and protein expression of phosphorylated (p)‑ERK1/2, Ki67, cleaved caspase‑3 and Bcl‑2 in intestinal tissues were determined via reverse transcription‑quantitative PCR and western blotting. Cell proliferation and apoptosis were also analysed via MTT assay and flow cytometry. In NEC mice, vitamin D reduced intestinal tissue damage, decreased the mRNA expression of IL‑6, IL‑1β and TNF‑α, and decreased the protein expression of cleaved caspase‑3 and MDA. Whereas, vitamin D increased the protein expression of Bcl‑2 and Ki67 and GPx, as well as the p‑ERK1/2/ERK1/2 ratio, in NEC mice. Furthermore, vitamin D improved cell viability, increased the ratio of p‑ERK1/2/ERK1/2, inhibited apoptosis, and decreased the mRNA expression of IL‑6, IL‑1β and TNF‑α in LPS‑treated IEC‑6 cells. The dual‑specificity mitogen‑activated protein kinase kinase inhibitor PD98059 reversed the effects of vitamin D on the proliferation, apoptosis and inflammation of LPS‑treated IEC‑6 cells. Overall, vitamin D relieved NEC in mice. Vitamin D promoted proliferation, and inhibited apoptosis and inflammation of LPS‑treated IEC‑6 cells by activating the ERK signalling pathway.

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