Gastric peroxisome proliferator activator receptor-gamma expression and cytoprotective actions of its ligands against ischemia-reperfusion injury in rats

摘要

The beneficial effects by peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on gastric injury induced by ischemia-reperfusion have been confirmed, however, the precise mechanism of its cytoprotection is not elucidated thoroughly. The aim of the present study was to determine the gastric localization of PPAR-gamma expression in the rat gastric mucosa, and to clarify the mechanism of its cytoprotective properties. The gastric expression of PPAR-gamma was confirmed by RT-PCR and western blot, and localized on gastric epithelial cells. The protective effect of PPAR-gamma ligands, pioglitazone or 15-deoxy-Delta(12,14)-prostaglandin J(2), on gastric ischemia-reperfusion injury was reversed by the co-administration with PPAR-gamma antagonist. The gastric expression of tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant-1 increased significantly in rats treated ischemia-reperfusion, and these increases were significantly inhibited by treatment with pioglitazone. Among the 1,032 probes, 18 probes were up-regulated at least 1.5-fold, 17 were down-regulated at least 1.5-fold by pioglitazone. The network including calnexin, endoplasmic reticulum stress protein, heat shock proteins, and proteasome genes was induced by pioglitazone treatment. In conclusion, activation of gastric epithelial PPAR-gamma receptor by its ligands may represent a novel therapeutic approach for gastric inflammation via up-regulation of heat shock proteins and endoplasmic reticulum-related proteins.