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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

Effect of pioglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) on acute gastric mucosal injury induced by ischemia-reperfusion (I-R) in rats. Multiple hemorrhagic erosions with acute edema developed in the glandular stomach of rats after 30-min ischemia and 60-min reperfusion, and pioglitazone (10 mg/kg) and 15d-PGJ2 (0.3 mg/kg) significantly inhibited the total area of gastric erosions induced by I-R. GW9662 significantly reversed the inhibition by these ligands against I-R-induced gastric injury. Data are expressed as mean (SEM) of 7 rats. #p<0.05 when compared to control rats treated with I-R, and +p<0.05 when compared to rats treated with I-R plus pioglitazone or dimethyl PGJ2.
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Figure 2: Effect of pioglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) on acute gastric mucosal injury induced by ischemia-reperfusion (I-R) in rats. Multiple hemorrhagic erosions with acute edema developed in the glandular stomach of rats after 30-min ischemia and 60-min reperfusion, and pioglitazone (10 mg/kg) and 15d-PGJ2 (0.3 mg/kg) significantly inhibited the total area of gastric erosions induced by I-R. GW9662 significantly reversed the inhibition by these ligands against I-R-induced gastric injury. Data are expressed as mean (SEM) of 7 rats. #p<0.05 when compared to control rats treated with I-R, and +p<0.05 when compared to rats treated with I-R plus pioglitazone or dimethyl PGJ2.

Mentions: According to our previous studies(14,18) in which pre-treatment with pioglitazone or 15d-PGJ2 1 h before the ischemia inhibited I-R-induced gastric mucosal injury in a dose-dependent manner, we used pioglitazone at a dose of 10 mg/kg and 15d-PGJ2 at a dose of 0.3 mg/kg and examined its pharmacological action in the present study. Neither ligand alone nor GW9662, a PPAR-γ antagonist, alone produced any macroscopic lesions in the rat stomach. I-R resulted in increase in total area of erosions developed in the glandular stomach. Both pioglitazone and 15d-PGJ2 significantly reduced the increase in total area of erosions after I-R, and the protective effect of these ligands was almost completely reversed by the co-administration with GW9662 (Fig. 2). The protective effect of pioglitazone and 15d-PGJ2 was confirmed histologically (data not shown). I-R resulted in large areas of epithelial crypt loss, predominantly neutrophilic infiltrate throughout the mucosa and submucosa, erosion, and mucosal bleeding. In contrast, pretreatment with pioglitazone or 15d-PGJ2 resulted in smaller erosions with few neutrophils.


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)

Effect of pioglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) on acute gastric mucosal injury induced by ischemia-reperfusion (I-R) in rats. Multiple hemorrhagic erosions with acute edema developed in the glandular stomach of rats after 30-min ischemia and 60-min reperfusion, and pioglitazone (10 mg/kg) and 15d-PGJ2 (0.3 mg/kg) significantly inhibited the total area of gastric erosions induced by I-R. GW9662 significantly reversed the inhibition by these ligands against I-R-induced gastric injury. Data are expressed as mean (SEM) of 7 rats. #p<0.05 when compared to control rats treated with I-R, and +p<0.05 when compared to rats treated with I-R plus pioglitazone or dimethyl PGJ2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effect of pioglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) on acute gastric mucosal injury induced by ischemia-reperfusion (I-R) in rats. Multiple hemorrhagic erosions with acute edema developed in the glandular stomach of rats after 30-min ischemia and 60-min reperfusion, and pioglitazone (10 mg/kg) and 15d-PGJ2 (0.3 mg/kg) significantly inhibited the total area of gastric erosions induced by I-R. GW9662 significantly reversed the inhibition by these ligands against I-R-induced gastric injury. Data are expressed as mean (SEM) of 7 rats. #p<0.05 when compared to control rats treated with I-R, and +p<0.05 when compared to rats treated with I-R plus pioglitazone or dimethyl PGJ2.
Mentions: According to our previous studies(14,18) in which pre-treatment with pioglitazone or 15d-PGJ2 1 h before the ischemia inhibited I-R-induced gastric mucosal injury in a dose-dependent manner, we used pioglitazone at a dose of 10 mg/kg and 15d-PGJ2 at a dose of 0.3 mg/kg and examined its pharmacological action in the present study. Neither ligand alone nor GW9662, a PPAR-γ antagonist, alone produced any macroscopic lesions in the rat stomach. I-R resulted in increase in total area of erosions developed in the glandular stomach. Both pioglitazone and 15d-PGJ2 significantly reduced the increase in total area of erosions after I-R, and the protective effect of these ligands was almost completely reversed by the co-administration with GW9662 (Fig. 2). The protective effect of pioglitazone and 15d-PGJ2 was confirmed histologically (data not shown). I-R resulted in large areas of epithelial crypt loss, predominantly neutrophilic infiltrate throughout the mucosa and submucosa, erosion, and mucosal bleeding. In contrast, pretreatment with pioglitazone or 15d-PGJ2 resulted in smaller erosions with few neutrophils.

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