Epidermal growth factor promotes intestinal secretory cell differentiation in weaning piglets via Wnt/β-catenin signalling

Abstract

Small intestinal epithelium homeostasis involves four principal cell types: enterocytes, goblet, enteroendocrine and Paneth cells. Epidermal growth factor (EGF) has been shown to affect enterocyte differentiation. This study determined the effect of dietary EGF on goblet, enteroendocrine and Paneth cell differentiation in piglet small intestine and potential mechanisms. Forty-two weaned piglets were used in a 2 × 3 factorial design; the major factors were time post-weaning (days 7 and 14) and dietary treatment (0, 200 or 400 µg/kg EGF supplementation). The numbers of goblet and enteroendocrine cells were generally greater with the increase in time post-weaning. Moreover, the supplementation of 200 µg/kg EGF increased (P < 0.01) the number of goblet and enteroendocrine cells in villus and crypt of the piglet small intestine as compared with the control. Dietary supplementation with 200 µg/kg EGF enhanced (P < 0.05) abundances of differentiation-related genes atonal homologue 1, mucin 2 and intestinal trefoil factor 3 messenger RNA (mRNA) as compared with the control. Piglets fed 200 or 400 µg/kg EGF diet had increased (P < 0.05) abundances of growth factor-independent 1, SAM pointed domain containing ETS transcription factor and pancreatic and duodenal homeobox 1 mRNA, but decreased the abundance (P < 0.01) of E74 like ETS transcription factor 3 mRNA as compared with the control. Animals receiving 400 µg/kg EGF diets had enhanced (P < 0.05) abundances of neurogenin3 and SRY-box containing gene 9 mRNA as compared with the control. The mRNA abundance and protein expression of lysozyme, a marker of Paneth cell, were also increased (P < 0.05) in those animals. As compared with the control, dietary supplementation with 200 µg/kg EGF increased the abundance of EGF receptor mRNA and the ratio of non-phospho(p)-β-catenin/β-catenin (P < 0.05) in villus epithelial cells at days 7 and 14. This ratio in crypt epithelial cells was higher (P < 0.05) on the both 200 and 400 µg/kg EGF groups during the same period. Our results demonstrated that dietary EGF stimulated goblet, enteroendocrine and Paneth cell differentiation in piglets during the post-weaning period, partly through EGFR and Wnt/β-catenin signalling.

Unveiling the Roles of Low-Density Lipoprotein Receptor-Related Protein 6 in Intestinal Homeostasis, Regeneration and Oncogenesis

“…This slight LRP5 increase could be sufficient to sustain enough Wnt signaling and maintain intestinal homeostasis and renewal in mice. Alternatively, additional factors such as fibroblast growth factors (FGF2 and FGF9) [ 23 ], glucagon-like pertide-2 [ 24 ], heparin-binding epidermal growth factor-like growth factor [ 25 ] and epidermal growth factor (EGF) [ 26 ] have been also shown to stimulate β-catenin signaling in intestinal crypts and thus, could compensate for the absence of LRP6 for the maintenance of intestinal homeostasis.…”

Dietary high protein-induced diarrhea and intestinal inflammation by activation of NF-κB signaling in piglets

“…Ileal and colonic tissues were ground into a fine powder over liquid nitrogen ( Zhou et al., 2012 ). Total RNA extraction, cDNA synthesis and real-time quantitative PCR (RT-qPCR) were conducted according to Wang et al. (2020a) .…”

Mechanisms of Epidermal Growth Factor Effect on Animal Intestinal Phosphate Absorption: A Review

“…The binding of EGF at the enterocytes surface induces dimerization of EGFR, which results in the activation of receptor tyrosine kinase (RTK) and RTK auto-phosphorylation, and subsequent activation of various signal transduction pathways, including mitogen-activated protein kinase (MAPK) ( 55 ), phosphoinositol 3 kinase (PI3K) ( 56 ), nuclear factor erythroid 2-related factor 2/ Kelch-like ECH-associated protein 1 (Nrf2/Keap1) ( 18 ), and mammalian target of rapamycin protein (mTOR) ( 57 ). Previous studies have demonstrated that EGF has many biological functions, including promoting intestinal repair ( 18 ) and nutrient absorption ( 23 , 58 , 59 ).…”

“…Epidermal growth factor (EGF), a small mitogenic polypeptide comprising 53 amino acid residues, has been established as a trophic factor for the epithelial cell homeostasis (17,18) and nutrient transport in the small intestine (19)(20)(21)(22)(23). Previous studies have reported that EGF inhibited the expression of NaPi-IIb (24)(25)(26)(27), which implied that EGF inhibited the active absorption of Pi.…”