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. 2022 Apr 14:2022:1322172.
doi: 10.1155/2022/1322172. eCollection 2022.

Reduced Incidence of Necrotizing Enterocolitis due to the Anti-Inflammatory Effects of CXCL14 in Intestinal Tissue

Xu Sun  1 , Lingqi Xu  1 , Shurong Ma  1 , Lulu Chen  1 , Ruze Tang  1 , Dashuang Li  1 , Fangjie Hu  1 , Ting Wang  1 , Yuan Gong  1 , Huiting Zhou  1 , Jian Wang  1
Affiliations

Reduced Incidence of Necrotizing Enterocolitis due to the Anti-Inflammatory Effects of CXCL14 in Intestinal Tissue

Xu Sun et al. J Healthc Eng. .

Retraction in

Abstract

Bioinformatic analysis indicated that downregulated CXCL14 will occur in the intestinal tissue of patients with necrotizing enterocolitis (NEC). To reveal the relationship between CXCL14 and mucosal immune regulation, we designed and implemented the experiments to explore the potential function of CXCL14 in the pathogenesis of NEC. Firstly, this study confirmed that the expression of CXCL14 decreased in the intestinal tract of NEC children. Secondly, the experiments results showed that CXCL14 could ameliorate the inflammatory injury of intestinal tissue through the suppressive effect on the expression of TNF-α and INF-γ in vivo. Finally, we explained that activation of the TLR4 can reduce the expression level of CXCL14 in the intestinal tissue of mouse pups. Collectively, our study suggested that CXCL14 may negatively regulate the inflammatory response in intestinal tissue and play an essential role in NEC development and progression.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
DEGs and pathway enrichment of GSE46619 dataset: (a) DEGs heatmap. (b) Volcano plot. (c) Pathway enrichment by GO/MF analysis. (d) Enrichment network analysis by GO/MF. (e) Details of the red box. (f) GSEA enrichment analysis associated with CXCL14 by GSE46619 dataset.
Figure 2
Figure 2
ScRNA-seq confirms that intestinal Stem cells could synthesize CXCL14: (a) UMAP of all small intestinal cells colored by cell type; (b) CXCL14 expression in different type of cells in A; (c) median percentage of major populations color coded to correspond to the major populations; (d) tSNE embedding showing rerun of cells from Nonimmune cell colored by clusters; (e) violin plots of CXCL14 gene expression level within each cluster showing cells; (f) tSNE of expression level of CXCL14 genes used in different patients.
Figure 3
Figure 3
CXCL14 was suppressed and pro-inflammatory factors were down-regulated in intestinal tissues of children with NEC. (a) Western blot of CXCL14 protein levels in intestine tissue of NEC patients and control (intestine atresia) patients. (b) Data are expressed as mean ± SD. ∗p < 0.05. (c) Immunofluorescence staining images of human intestine tissue (NEC vs. intestine atresia as control, magnification, 100×; Bar = 100 μm).
Figure 4
Figure 4
CXCL14 expression in vivo. (a) ELISA test. (b) mRNA expression; (c) intestine organoid and Caco2 cell culture; (d) the number of organoids per image; (e) CXCL14 in supernatant; (f) mRNA.
Figure 5
Figure 5
Intestinal tissue results concerning the inhibition of inflammatory response in intraperitoneal injection of CXCL14 mice. (a) Survival rate of each group. (b) Ileum of each group. (c) HE staining and Immunofluorescence staining of TNF-α and IFN-γ in each group (magnification, 200×; bar = 200 μm).
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