PPARgamma mediates NSAIDs-induced upregulation of TFF2 expression in gastric epithelial cells.
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).
Shimada
Tadahito
T
Department of Gastroenterology and Institute for Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. tshimada@dokkyomed.ac.jp
Koitabashi
Ayako
A
Fujii
Yoichiro
Y
Hashimoto
Takashi
T
Hosaka
Kumi
K
Tabei
Kyoko
K
Namatame
Takashi
T
Yoneda
Masashi
M
Hiraishi
Hideyuki
H
Terano
Akira
A
D000813:Anilides / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D015854:Up-Regulation / Q000187:drug effects*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D014157:Transcription Factors; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D001241:Aspirin; D007213:Indomethacin