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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 on CINC-1 contents (A), TNF-α contents (B), the gastric expression of CINC-1/TNF-α mRNA determined RT-PCR (C), and CINC-1 production from RGM-1 cells stimulated by anoxia-reoxygenation (D). The concentration of CINC-1/TNF-α in the supernatant of mucosal homogenates was determined by ELISA kit specific for rat CINC-1 and rat TNF-α. (A, B); Value reported as the mean ± SE of 6 to 8 rats. †p<0.01 when compared to sham-operated rats receiving 0.5% CMC solution (vehicle) alone, and #p<0.05 when compared to rats receiving vehicle plus ischemia-reperfusion (I-R). (C); A representative 2% agarose gel of RT-PCR products for CINC-1 and TNF-α mRNA is shown, also including β-actin mRNA. (D); †p<0.01 when compared to normoxia (N), and #p<0.05 when compared to anoxia-reoxygenation (A/R).
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Figure 3: Effect of pioglitazone on CINC-1 contents (A), TNF-α contents (B), the gastric expression of CINC-1/TNF-α mRNA determined RT-PCR (C), and CINC-1 production from RGM-1 cells stimulated by anoxia-reoxygenation (D). The concentration of CINC-1/TNF-α in the supernatant of mucosal homogenates was determined by ELISA kit specific for rat CINC-1 and rat TNF-α. (A, B); Value reported as the mean ± SE of 6 to 8 rats. †p<0.01 when compared to sham-operated rats receiving 0.5% CMC solution (vehicle) alone, and #p<0.05 when compared to rats receiving vehicle plus ischemia-reperfusion (I-R). (C); A representative 2% agarose gel of RT-PCR products for CINC-1 and TNF-α mRNA is shown, also including β-actin mRNA. (D); †p<0.01 when compared to normoxia (N), and #p<0.05 when compared to anoxia-reoxygenation (A/R).

Mentions: To test if pioglitazone treatment could modulate the inflammatory response through regulation of cytokine production, we analyzed gastric mucosal levels of TNF-α and CINC-1. The gastric concentrations of TNF-α and CINC-1 increased significantly in rats treated I-R, and these increases were significantly inhibited by treatment with pioglitazone at a dose of 10 mg/kg (Fig. 3 a and b). To further confirm the inhibitory effect of pioglitazone on TNF-α and CINC-1 production, we analyzed gastric expression of TNF-α and CINC-1 using RT-PCR yielding 225 and 907 base pair products to identify TNF-α and CINC-1 gene expression, respectively. As shown in Fig. 3c, we found the expression of these genes in the rat treated with sham-operation to be negligible or faint. In contrast, transcription was readily shown in I-R-treated rats. Treatment with pioglitazone suppressed mRNA expression for each gene. In addition, pioglitazone markedly inhibited the CINC-1 production from RGM-1 cells stimulated by 2 h-anoxia and 6 h-reoxygenation (Fig. 3d).


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 on CINC-1 contents (A), TNF-α contents (B), the gastric expression of CINC-1/TNF-α mRNA determined RT-PCR (C), and CINC-1 production from RGM-1 cells stimulated by anoxia-reoxygenation (D). The concentration of CINC-1/TNF-α in the supernatant of mucosal homogenates was determined by ELISA kit specific for rat CINC-1 and rat TNF-α. (A, B); Value reported as the mean ± SE of 6 to 8 rats. †p<0.01 when compared to sham-operated rats receiving 0.5% CMC solution (vehicle) alone, and #p<0.05 when compared to rats receiving vehicle plus ischemia-reperfusion (I-R). (C); A representative 2% agarose gel of RT-PCR products for CINC-1 and TNF-α mRNA is shown, also including β-actin mRNA. (D); †p<0.01 when compared to normoxia (N), and #p<0.05 when compared to anoxia-reoxygenation (A/R).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3045692&req=5

Figure 3: Effect of pioglitazone on CINC-1 contents (A), TNF-α contents (B), the gastric expression of CINC-1/TNF-α mRNA determined RT-PCR (C), and CINC-1 production from RGM-1 cells stimulated by anoxia-reoxygenation (D). The concentration of CINC-1/TNF-α in the supernatant of mucosal homogenates was determined by ELISA kit specific for rat CINC-1 and rat TNF-α. (A, B); Value reported as the mean ± SE of 6 to 8 rats. †p<0.01 when compared to sham-operated rats receiving 0.5% CMC solution (vehicle) alone, and #p<0.05 when compared to rats receiving vehicle plus ischemia-reperfusion (I-R). (C); A representative 2% agarose gel of RT-PCR products for CINC-1 and TNF-α mRNA is shown, also including β-actin mRNA. (D); †p<0.01 when compared to normoxia (N), and #p<0.05 when compared to anoxia-reoxygenation (A/R).
Mentions: To test if pioglitazone treatment could modulate the inflammatory response through regulation of cytokine production, we analyzed gastric mucosal levels of TNF-α and CINC-1. The gastric concentrations of TNF-α and CINC-1 increased significantly in rats treated I-R, and these increases were significantly inhibited by treatment with pioglitazone at a dose of 10 mg/kg (Fig. 3 a and b). To further confirm the inhibitory effect of pioglitazone on TNF-α and CINC-1 production, we analyzed gastric expression of TNF-α and CINC-1 using RT-PCR yielding 225 and 907 base pair products to identify TNF-α and CINC-1 gene expression, respectively. As shown in Fig. 3c, we found the expression of these genes in the rat treated with sham-operation to be negligible or faint. In contrast, transcription was readily shown in I-R-treated rats. Treatment with pioglitazone suppressed mRNA expression for each gene. In addition, pioglitazone markedly inhibited the CINC-1 production from RGM-1 cells stimulated by 2 h-anoxia and 6 h-reoxygenation (Fig. 3d).

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