PPARgamma mediates NSAIDs-induced upregulation of TFF2 expression in gastric epithelial cells

Tadahito Shimada; Ayako Koitabashi; Yoichiro Fujii; Takashi Hashimoto; Kumi Hosaka; Kyoko Tabei; Takashi Namatame; Masashi Yoneda; Hideyuki Hiraishi; Akira Terano

doi:10.1016/S0014-5793(03)01527-8

PPARgamma mediates NSAIDs-induced upregulation of TFF2 expression in gastric epithelial cells

FEBS Lett. 2004 Jan 30;558(1-3):33-8. doi: 10.1016/S0014-5793(03)01527-8.

Authors

Tadahito Shimada¹, Ayako Koitabashi, Yoichiro Fujii, Takashi Hashimoto, Kumi Hosaka, Kyoko Tabei, Takashi Namatame, Masashi Yoneda, Hideyuki Hiraishi, Akira Terano

Affiliation

¹ Department of Gastroenterology and Institute for Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. [email protected]

PMID: 14759512
DOI: 10.1016/S0014-5793(03)01527-8

Abstract

Trefoil factor family (TFF) is a group of peptides that play critical roles in maintaining gastric mucosal integrity. In real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and reporter gene assays, we show that indomethacin and aspirin upregulate TFF2 expression in MKN45 gastric cells. These drugs also activated peroxisome proliferator-activated receptor gamma (PPARgamma) at concentration ranges that increase TFF2 expression, and upregulated TFF2 expression was suppressed by GW9662, a specific inhibitor of PPARgamma. These results suggest that indomethacin and aspirin upregulate gastric expression of TFF2 through activation of PPARgamma. This mechanism may be important in reducing the extent of gastric mucosal injury caused by the administration of non-steroidal anti-inflammatory drugs (NSAIDs).

MeSH terms

Anilides / pharmacology
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Aspirin / pharmacology
Cell Line, Tumor
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Epithelial Cells / drug effects
Epithelial Cells / metabolism*
Gene Expression Regulation, Neoplastic
Genes, Reporter
Humans
Indomethacin / pharmacology
Mucins*
Muscle Proteins*
Neuropeptides*
Peptides / metabolism*
RNA, Messenger / metabolism
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Stomach Neoplasms / pathology
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcription, Genetic / drug effects
Transcriptional Activation / drug effects
Trefoil Factor-2
Trefoil Factor-3
Up-Regulation / drug effects*

Substances

2-chloro-5-nitrobenzanilide
Anilides
Anti-Inflammatory Agents, Non-Steroidal
Enzyme Inhibitors
Mucins
Muscle Proteins
Neuropeptides
Peptides
RNA, Messenger
Receptors, Cytoplasmic and Nuclear
TFF2 protein, human
TFF3 protein, rat
Tff2 protein, rat
Transcription Factors
Trefoil Factor-2
Trefoil Factor-3
Aspirin
Indomethacin