Effect of PPARgamma ligands on the viability of gastric epithelial cells.
BACKGROUND
[corrected] Peroxisome proliferator-activated receptors (PPAR) are a family of three nuclear receptors (PPARalpha, PPARdelta, and PPARgamma). Although recent evidence suggests a role for PPARgamma in the regulation of colonic epithelial cell growth, the role for PPARgamma in the stomach has not been established.


OBJECTIVE
To examine the expression of PPARgamma and the effects of PPARgamma ligands on the viability of gastric epithelial cells.


METHODS
MKN45 cells and primary cultured rat gastric epithelial cells were used. Troglitazone (TGZ) and 15-deoxy-Delta12, 14-prostaglandin J2 (15d-PGJ2) were used as PPARgamma ligands. Expression of PPARgamma was examined by RT-PCR and Western blot analysis. Cell viability was measured by WST-1 assay and TUNEL assay was performed to detect apoptosis.


RESULTS
MKN45 cells expressed all subtypes of PPAR. PPARgamma ligands decreased cell viability and induced cell death in a dose-dependent manner, whereas ligands for PPARalpha and PPARdelta had no significant effect. TUNEL assay showed that this cell death is apoptosis. Primary cultured rat gastric epithelial cells also expressed PPARgamma and activation of PPARgamma decreased cell viability.


CONCLUSIONS
These results suggest that PPARgamma plays an important role in the regulation of cell growth and cell death in gastric epithelial cells.
Kojima
K
K
Department of Gastroenterology, Dokkyo University School of Medicine, Tochigi, Japan.
Shimada
T
T
Mitobe
Y
Y
Yoshiura
K
K
Hiraishi
H
H
Terano
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008024:Ligands; D008858:Microscopy, Phase-Contrast; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000096:biosynthesis*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002839:Chromans; D018076:DNA, Complementary; D007155:Immunologic Factors; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone; D015230:Prostaglandin D2