Downregulation of prostaglandin E2 is involved in hindgut mucosal damage in lactating goats fed a high-concentrate diet

Abstract

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 E2 synthesis and the downstream signalling pathways. What is the main finding and its importance? The downregulation of local prostaglandin E2 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 E2 (PGE2 ) 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, PGE2 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 PGE2 content and EP4 (PGE2 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 PGE2 synthesis and its downstream signalling pathway.