ERK1/2 mitogen-activated protein kinase mediates downregulation of intestinal tight junction proteins in heat stress-induced IBD model in pig

In many mammalian species, including pigs, heat stress (HS) detrimentally leads to epithelium damage and increases intestinal permeability. However, the underlying molecular mechanisms are not thoroughly investigated yet. This study aimed to examine the RIP1/RIP3-ERK1/2 signaling pathway that regulates the expression of tight junction proteins in HS-treated pigs. In in vitro cultured intestinal porcine epithelial cells (IPEC-J2), HS induced the expression of tight junction proteins, ZO-1, claudin-1, and claudin-4, that are regulated by the ERK1/2-MAPK signaling pathway. Further, high expression of HSP70 in IPEC-J2 cells induced a significant decrease in receptor-interacting protein 1/3 (RIP1/3), phosphorylated ERK, and tight junction protein claudin-1 (P