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

Naito Y, Takagi T, Katada K, Tomatsuri N, Mizushima K, Handa O, Kokura S, Yagi N, Ichikawa H, Yoshikawa T - J Clin Biochem Nutr (2011)

Bottom Line: The gastric expression of tumor necrosis factor-α and cytokine-induced neutrophil chemoattractant-1 increased significantly in rats treated ischemia-reperfusion, and these increases were significantly inhibited by treatment with 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-γ 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.

ABSTRACT
The beneficial effects by peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-γ expression in the rat gastric mucosa, and to clarify the mechanism of its cytoprotective properties. The gastric expression of PPAR-γ was confirmed by RT-PCR and western blot, and localized on gastric epithelial cells. The protective effect of PPAR-γ ligands, pioglitazone or 15-deoxy-Δ(12,14)-prostaglandin J(2), on gastric ischemia-reperfusion injury was reversed by the co-administration with PPAR-γ antagonist. The gastric expression of tumor necrosis factor-α 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-γ 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.

No MeSH data available.


Related in: MedlinePlus

A network of genes commonly regulated after pioglitazone treatment. Seven genes that were up-regulated in pioglitazone-treated stomach were analyzed by the Ingenuity Pathway Analysis tool. The shown major network that was found to be significantly up-regulated by pioglitazone was associated with cell cycle, cell-to-cell signaling and interaction, and cancer. Shaded genes are the genes identified by microarray analysis and others are those associated with the regulated genes based on the pathway analysis. The meaning of the node shapes is also indicated. Asterisks indicate genes that were identified multiple times.
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Figure 4: A network of genes commonly regulated after pioglitazone treatment. Seven genes that were up-regulated in pioglitazone-treated stomach were analyzed by the Ingenuity Pathway Analysis tool. The shown major network that was found to be significantly up-regulated by pioglitazone was associated with cell cycle, cell-to-cell signaling and interaction, and cancer. Shaded genes are the genes identified by microarray analysis and others are those associated with the regulated genes based on the pathway analysis. The meaning of the node shapes is also indicated. Asterisks indicate genes that were identified multiple times.

Mentions: We next asked what genes are modulated following treatment of gastric mucosa with pioglitazone and if there are differences between the affected gene networks in pioglitazone-treated mucosa compared to non-treated mucosa. Among the 1,032 probes (Rat Toxicology U34 array, Affymetrix), the number of genes, the expression levels of which increased or decreased more than 1.5-fold in pioglitazone-treated mucosa, was 35 including 10 ESTs. 18 probes were up-regulated and 17 were down-regulated (Table 1). Table 2 showed a gene network affected by pioglitazone, which obtained a most highest score (score 14) as defined by the Pathway Analysis, and Fig. 4 demonstrated the associated network that was significantly affected by pioglitazone. The shown network was significantly associated with cell cycle, cell-to-cell signaling and interaction, and cancer. This network included CANX, ERP70, heat-shock protein 60 (HSP60), HSPA5, HSPCA, and PSMB4 genes.


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

Naito Y, Takagi T, Katada K, Tomatsuri N, Mizushima K, Handa O, Kokura S, Yagi N, Ichikawa H, Yoshikawa T - J Clin Biochem Nutr (2011)

A network of genes commonly regulated after pioglitazone treatment. Seven genes that were up-regulated in pioglitazone-treated stomach were analyzed by the Ingenuity Pathway Analysis tool. The shown major network that was found to be significantly up-regulated by pioglitazone was associated with cell cycle, cell-to-cell signaling and interaction, and cancer. Shaded genes are the genes identified by microarray analysis and others are those associated with the regulated genes based on the pathway analysis. The meaning of the node shapes is also indicated. Asterisks indicate genes that were identified multiple times.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045692&req=5

Figure 4: A network of genes commonly regulated after pioglitazone treatment. Seven genes that were up-regulated in pioglitazone-treated stomach were analyzed by the Ingenuity Pathway Analysis tool. The shown major network that was found to be significantly up-regulated by pioglitazone was associated with cell cycle, cell-to-cell signaling and interaction, and cancer. Shaded genes are the genes identified by microarray analysis and others are those associated with the regulated genes based on the pathway analysis. The meaning of the node shapes is also indicated. Asterisks indicate genes that were identified multiple times.
Mentions: We next asked what genes are modulated following treatment of gastric mucosa with pioglitazone and if there are differences between the affected gene networks in pioglitazone-treated mucosa compared to non-treated mucosa. Among the 1,032 probes (Rat Toxicology U34 array, Affymetrix), the number of genes, the expression levels of which increased or decreased more than 1.5-fold in pioglitazone-treated mucosa, was 35 including 10 ESTs. 18 probes were up-regulated and 17 were down-regulated (Table 1). Table 2 showed a gene network affected by pioglitazone, which obtained a most highest score (score 14) as defined by the Pathway Analysis, and Fig. 4 demonstrated the associated network that was significantly affected by pioglitazone. The shown network was significantly associated with cell cycle, cell-to-cell signaling and interaction, and cancer. This network included CANX, ERP70, heat-shock protein 60 (HSP60), HSPA5, HSPCA, and PSMB4 genes.

Bottom Line: The gastric expression of tumor necrosis factor-α and cytokine-induced neutrophil chemoattractant-1 increased significantly in rats treated ischemia-reperfusion, and these increases were significantly inhibited by treatment with 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-γ 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.

ABSTRACT
The beneficial effects by peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-γ expression in the rat gastric mucosa, and to clarify the mechanism of its cytoprotective properties. The gastric expression of PPAR-γ was confirmed by RT-PCR and western blot, and localized on gastric epithelial cells. The protective effect of PPAR-γ ligands, pioglitazone or 15-deoxy-Δ(12,14)-prostaglandin J(2), on gastric ischemia-reperfusion injury was reversed by the co-administration with PPAR-γ antagonist. The gastric expression of tumor necrosis factor-α 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-γ 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.

No MeSH data available.


Related in: MedlinePlus