New insights into the unfolded protein response (UPR)-anterior gradient 2 (AGR2) pathway in the regulation of intestinal barrier function in weaned piglets

Sustained dysfunction of the intestinal barrier caused by early weaning is a major factor that induces postweaning diarrhea in weaned piglets. In both healthy and diseased states, the intestinal barrier is regulated by goblet cells. Alterations in the characteristics of goblet cells are linked to intestinal barrier dysfunction and inflammatory conditions during pathogenic infections. In this review, we summarize the current understanding of the mechanisms of the unfolded protein response (UPR) and anterior gradient 2 (AGR2) in maintaining intestinal barrier function and how modifications to these systems affect mucus barrier characteristics and goblet cell dysregulation. We highlight a novel mechanism underlying the UPR-AGR2 pathway, which affects goblet cell differentiation and maturation and the synthesis and secretion of mucin by regulating epidermal growth factor receptor and mucin 2. This study provides a theoretical basis and new insights into the regulation of intestinal health in weaned piglets.