Abstract
Most alterations during weaning involve physiological changes in intestinal structure and function. Here, we evaluated the molecular mechanisms regulating the effects of nucleotides on weaning. Nucleotide treatment induced Trefoil factor 3 (TFF3) expression and IPEC-J2 cell growth and reduced wound width. Treatment with nucleosides and TFF3 in lipopolysaccharide-challenged IPEC-J2 cells increased intestinal transepithelial electrical resistance and decreased intestinal permeability. Additionally, nucleosides improved intestinal barrier function through induction of TFF3-mediated phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase 1/2, p38, and Janus kinase/signal transducer and activator of transcription signaling pathways. Among selected differentially expressed genes, SAM pointed domain containing ETS transcription factor (SPDEF) expression was elevated by nucleotides in a concentration-dependent manner. Moreover, SPDEF directly regulated TFF3 expression via binding to the promoter. In vivo, nucleotide supplementation improved growth performance, serum stress levels, and intestinal morphology. Our findings provide insights into the molecular mechanisms of intestinal development during weaning in pigs.
Highlights
The suckling to weaning transition is one of the most stressful events in pig development; pigs experience significant physiological, environmental, and social challenges that can contribute to intestinal and immune system dysfunction, resulting in reduced pig health, growth, and feed intake[1,2]
In the present study, we investigated the gene expression profiles in intestinal tissue with or without NT treatment and identified 748 annotated differentially expressed genes (DEGs) in the weaning transition. Among these DEGs, we selected Trefoil factor 3 (TFF3), the intestinal trefoil factor; TFF3 is a peptide secreted from the normal mucous epithelium and is synthesized in mucin-producing cells, such as goblet cells, in the intestinal epithelium[15]
We identified genes that were affected by dietary NT supplementation and further investigated the effects of exogenous NT treatment on TFF3-mediated functions in intestinal epithelial cells
Summary
The suckling to weaning transition is one of the most stressful events in pig development; pigs experience significant physiological, environmental, and social challenges that can contribute to intestinal and immune system dysfunction, resulting in reduced pig health, growth, and feed intake[1,2]. One of the most dramatic alterations mediating the weaning transition is physiological changes in the structure and function of the intestine, including shortening of the villi (villous atrophy) and increased crypt depth (crypt elongation) during the weaning transition[2,6]. These physiological changes can impact the function of the small intestine, including digestion, absorption, secretion, and maintenance of barrier function, which may contribute to postweaning growth[1].
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