Our results suggest that maternal dietary betaine supplementation during gestation suppresses GALK1 expression in the liver of neonatal piglets, which involves complex gene regulation mechanisms including DNA methylation, histone modification, miRNAs expression and SP1-mediated transcriptional modulation.
New Findings r What is the central question of this study?A high-concentrate (HC) diet results in damage to the hindgut mucosa. The aim of the study was to investigate the status of epithelial proliferation in the hindgut mucosa of goats with subacute ruminal acidosis and, simultaneously, to evaluate prostaglandin E 2 synthesis and the downstream signalling pathways. r What is the main finding and its importance?The downregulation of local prostaglandin E 2 synthesis and its downstream signalling pathway are involved in the process of inhibiting epithelial proliferation in the hindgut epithelium of HC-fed goats. Our results provide new insight into the relationship between abnormal fermentation in the hindgut and damage to the intestinal mucosal barrier. Our previous data demonstrated that feeding a high-concentrate (HC) diet to lactating goats for a long time causes severe damage to the hindgut mucosa and parallels the activation of cell apoptosis and local oxidative stress. In the present study, changes in production of prostaglandin E 2 (PGE 2 ) and its signalling pathway were evaluated in the process of epithelial barrier disruption in the hindgut. Twelve goats in mid-lactation were randomly assigned to either a HC diet group or a low-concentrate (LC) diet group for 10 weeks. Cell proliferation markers, cyclooxygenase-2 activity, PGE 2 content and the relative signalling pathway, including CREB and AKT, were analysed by enzyme-linked immunosorbent assay and Western blot, respectively. The mRNA and protein expressions of MKI67 and CCND2 (two proliferation markers) were significantly decreased in the caecal mucosa of HC-compared with LC-fed goats (P < 0.05). The protein content of interleukin-10 and β-defensin in the caecal mucosa was also downregulated in HC-fed goats (P < 0.05). The HC-fed goats showed a tendency to a decrease in cyclooxygenase-2 enzyme activity (P = 0.081) and a significant decrease of local PGE 2 content and EP4 (PGE 2 receptor) protein expression in caecal mucosa (P < 0.05). Moreover, the protein abundance of p-CREB (P = 0.069) and p-AKT (P < 0.05) and the mRNA expression of epidermal growth factor receptor (P < 0.05) were downregulated in caecal mucosa of HC-compared with LC-fed goats. These results indicate that a reduction in epithelial cell proliferation was partly responsible for the damage to the epithelial barrier, which might be associated with the downregulation of PGE 2 synthesis and its downstream signalling pathway. (Gaebel et al. 1989;Plaizier et al. 2008;Steele et al. 2011;Li et al. 2012;Liu et al. 2013) and can even cause inflammatory responses because of the accumulation of bacterial endotoxins (lipopolysaccharide; LPS) derived from Gram-negative bacteria residing in the rumen and hindgut (Khafipour et al. 2009;Zebeli & Ametaj, 2009). In comparison to the histological structure of the rumen, which has multilayered squamous epithelium, the hindgut, which is another region where microbial fermentation occurs, is more 'leaky' , being covered by a single layer of epithelial c...
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