Up-regulation of TFF expression by PPARgamma ligands in gastric epithelial cells.
BACKGROUND
Although trefoil factor family peptides (TFF peptides) are assumed to play important roles in gastric mucosal protection, the regulatory mechanism of gastric TFF expression has not been fully understood yet. Recent reports showed gastric expression of peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor known to be involved in the regulation of cell growth and differentiation in other cell types, such as adipocytes.


OBJECTIVE
To determine whether PPARgamma affects the expression of TFF in gastric epithelial cells.


METHODS
MKN45 gastric cells were used as a model of gastric epithelial cells. DNA synthesis of the cells was determined by the measurement of BrdU incorporation. The effects of PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) on TFF expression were assessed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
MKN45 cells expressed a significant amount of PPARgamma. Both 15d-PGJ2 and TGZ suppressed DNA synthesis of the cells in a dose-dependent manner. In the control condition, MKN45 cells most abundantly expressed TFF1 and the relative expression level of TFF1, TFF2, and TFF3 mRNA was 1700:32:1. TFF1 and TFF2 mRNA levels were significantly up-regulated by the incubation of the cells with 15d-PGJ2 (10 micro m) or TGZ (30 micro m), whereas TFF3 mRNA level was not affected.


CONCLUSIONS
The results of the present study suggest a possible role of PPARgamma in the regulation of TFF expression in gastric epithelial cells.
Shimada
T
T
Department of Gastroenterology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. tshimada@dokkyomed.ac.jp
Koitabashi
A
A
Kuniyoshi
T
T
Hashimoto
T
T
Yoshiura
K
K
Yoneda
M
M
Hiraishi
H
H
Terano
A
A
D015153:Blotting, Western; D002455:Cell Division; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D056918:Nuclear Receptor Coactivators; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006133:Growth Substances; D047908:Intracellular Signaling Peptides and Proteins; D009077:Mucins; D009124:Muscle Proteins; C486559:NCOA6 protein, human; D009479:Neuropeptides; D056918:Nuclear Receptor Coactivators; D010455:Peptides; D012333:RNA, Messenger; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D014157:Transcription Factors; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3