Shimada Tadahito, Koitabashi Ayako, Fujii Yoichiro, Hashimoto Takashi, Hosaka Kumi, Tabei Kyoko, Namatame Takashi, Yoneda Masashi, Hiraishi Hideyuki, Terano Akira
Department of Gastroenterology and Institute for Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan.
FEBS Lett. 2004 Jan 30;558(1-3):33-8. doi: 10.1016/S0014-5793(03)01527-8.
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).
三叶因子家族(TFF)是一组在维持胃黏膜完整性中起关键作用的肽。在实时定量逆转录-聚合酶链反应(RT-PCR)和报告基因检测中,我们发现吲哚美辛和阿司匹林可上调MKN45胃细胞中TFF2的表达。这些药物在增加TFF2表达的浓度范围内还激活了过氧化物酶体增殖物激活受体γ(PPARγ),而PPARγ的特异性抑制剂GW9662可抑制TFF2表达的上调。这些结果表明,吲哚美辛和阿司匹林通过激活PPARγ上调胃中TFF2的表达。该机制可能在减轻非甾体抗炎药(NSAIDs)给药引起的胃黏膜损伤程度方面具有重要意义。