Developmental Changes of TGF-β1 and Smads Signaling Pathway in Intestinal Adaption of Weaned Pigs

Abstract

Weaning stress caused marked changes in intestinal structure and function. Transforming growth factor-β1 (TGF-β1) and canonical Smads signaling pathway are suspected to play an important regulatory role in post-weaning adaptation of the small intestine. In the present study, the intestinal morphology and permeability, developmental expressions of tight junction proteins and TGF-β1 in the intestine of piglets during the 2 weeks after weaning were assessed. The expressions of TGF-β receptor I/II (TβRI, TβRII), smad2/3, smad4 and smad7 were determined to investigate whether canonical smads signaling pathways were involved in early weaning adaption process. The results showed that a shorter villus and deeper crypt were observed on d 3 and d 7 postweaning and intestinal morphology recovered to preweaning values on d 14 postweaning. Early weaning increased (P<0.05) plasma level of diamine oxidase (DAO) and decreased DAO activities (P<0.05) in intestinal mucosa on d 3 and d 7 post-weaning. Compared with the pre-weaning stage (d 0), tight junction proteins level of occludin and claudin-1 were reduced (P<0.05) on d 3, 7 and 14 post-weaning, and ZO-1 protein was reduced (P<0.05) on d 3 and d 7 post-weaning. An increase (P<0.05) of TGF-β1 in intestinal mucosa was observed on d 3 and d 7 and then level down on d 14 post-weaning. Although there was an increase (P<0.05) of TβR II protein expression in the intestinal mucosa on d3 and d 7, no significant increase of mRNA of TβRI, TβRII, smad2/3, smad4 and smad7 was observed during postweaning. The results indicated that TGF-β1 was associated with the restoration of intestinal morphology and barrier function following weaning stress. The increased intestinal endogenous TGF-β1 didn't activate the canonical Smads signaling pathway.

Effect of weaning age on intestinal mucosal morphology, permeability, gene expression of tight junction proteins, cytokines and secretory IgA in Wuzhishan mini piglets

“…The intestinal barrier is mainly formed by the intercellular tight junctions together with a layer of columnar epithelium . Prior studies have demonstrated that early weaning could cause sustained dysfunction of the intestinal barrier, which is characterised by decreased expression of tight junction proteins Xiao et al 2014). The mRNA levels of occludin and ZO-1 in jejunal mucosa as well as occludin, ZO-1, and claudin in ileal mucosa were lower in 21W group than 35W and 42W groups in this study.…”

“…Plasma DAO activity and D-lactate level are useful markers to evaluate the extent of damage and repair of intestinal mucosa (Murray et al 1993;Wu et al 1996). These two markers are negatively related to the intestinal permeability, and will increase when intestinal permeability is damaged due to weaning or other stresses (Xiao et al 2014). In the present study, DAO activities and D-lactate levels were significantly increased at 28 to 35 days old in 21W group compared with 35W and 42W groups.…”

Copper/zinc-loaded montmorillonite influences intestinal integrity, the expression of genes associated with inflammation, TLR4–MyD88 and TGF-β1 signaling pathways in weaned pigs after LPS challenge

“…33 It has been reported that most of the cytokines promote epithelial restitution through a TGF-b-dependent mechanism. 21 Xiao et al 16 found that the TGF-b1 was associated with the restoration of intestinal morphology and barrier function in weaning piglets. Shiou et al 34 reported that oral administration of TGF-b1 reduces the incidence of necrotizing enterocolitis through an immune suppressive effect directly on intestinal epithelium in vivo and decreased systemic IL-6 and IFN-a levels.…”

“…14,15 Moreover, a previous study has demonstrated the role of TGF-b1 in the restoration of barrier integrity. 16 Accordingly, the purpose of this research was to investigate whether supplemental Cu/Zn-Mt could improve the intestinal epithelial barrier by regulating the expression of genes associated with inflammation in weaned pigs after Escherichia coli LPS challenge. In this study, E. coli LPS, a potent endotoxin, was administered to build the model of intestinal injury.…”

Effects of zinc-exchanged montmorillonite with different zinc loading capacities on growth performance, intestinal microbiota, morphology and permeability in weaned piglets

“…Weaning is the most significant event in the life of pigs and weaning process is commonly associated with microbial imbalance and intestinal barrier dysfunction, which are responsible for the stunted growth and diarrhea observed in the first 2 weeks after weaning (Moeser et al, 2007;Hu et al, 2013c;Xiao et al, 2014). Feeding pharmacological level of Zn (2000-4000 mg/kg) is used in the pig industry to alleviate post-weaning diarrhea and improve performance .…”