title: PPARgamma mediates NSAIDs-induced upregulation of TFF2 expression in gastric epithelial cells.
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).
authors.affiliation: Department of Gastroenterology and Institute for Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. tshimada@dokkyomed.ac.jp
authors.forename: Tadahito
authors.initials: T
authors.lastname: Shimada
authors.forename: Ayako
authors.initials: A
authors.lastname: Koitabashi
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Fujii
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Kumi
authors.initials: K
authors.lastname: Hosaka
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tabei
authors.forename: Takashi
authors.initials: T
authors.lastname: Namatame
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoneda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hiraishi
authors.forename: Akira
authors.initials: A
authors.lastname: Terano
mesh_terms: 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*
chemical_list: 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