Nucleotide-mediated SPDEF modulates TFF3-mediated wound healing and intestinal barrier function during the weaning process

• Published in: Scientific reports 2018-03, Vol.8 (1), p.4827-13, Article 4827
• Main Authors: Lee, Sang In, Kim, In Ho
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/337/2019; 631/601/1737; AKT protein; ETS protein; Extracellular signal-regulated kinase; Humanities and Social Sciences; Intestine; Janus kinase; Lipopolysaccharides; Molecular modelling; multidisciplinary; Nucleosides; Nucleotides; Permeability; Science; Science (multidisciplinary); Small intestine; Structure-function relationships; Supplements; Trefoil factor; Weaning; Wound healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-23218-4

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.