PPARgamma physiology and pathology in gastrointestinal epithelial cells.
PPARgamma physiology and pathology in gastrointestinal epithelial cells.
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作者：
E. Thompson
过氧化物酶体增殖物激活受体-γ（PPARgamma）在胃肠道上皮中以非常高的水平表达。PPARgamma在胃肠道上皮细胞中的许多功能近年来已被阐明，并且正在出现一种模式，表明该受体在胃肠道生理学中起重要作用。还有强有力的证据表明，在散发性结肠癌的临床前啮齿动物模型中，PPARgamma是结肠癌抑制因子，并且对开发PPARgamma激动剂作为结肠癌的预防剂或化学预防剂有相当大的兴趣。在小鼠和人结肠癌细胞系中的研究表明了可能解释PPARgamma激动剂的肿瘤抑制作用的几种机制，尽管在所有情况下都不清楚这些作用是否完全由PPARgamma介导。相反，一些报告表明，PPARgamma激动剂在某些情况下可能促进结肠癌。这种可能性值得高度关注，因为数百万II型糖尿病患者目前正在服用PPARgamma激动剂。这篇综述将集中在最近的数据有关的四个关键问题：什么是PPARgamma在胃肠道上皮细胞的生理功能; PPARgamma如何抑制结肠癌的发生;是PPARgamma的肿瘤促进剂;什么是PPARgamma在结肠癌预防的未来？
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed at very high levels in the gastrointestinal epithelium. Many of the functions of PPARgamma in gastrointestinal epithelial cells have been elucidated in recent years, and a pattern is emerging which suggests that this receptor plays an important role in gastrointestinal physiology. There is also strong evidence that PPARgamma is a colon cancer suppressor in pre-clinical rodent models of sporadic colon cancer, and there is considerable interest in exploitation of PPARgamma agonists as prophylactic or chemopreventive agents in colon cancer. Studies in mice and in human colon cancer cell lines suggest several mechanisms that might account for the tumor suppressive effects of PPARgamma agonists, although it is not in all cases clear whether these effects are altogether mediated by PPARgamma. Conversely, several reports suggest that PPARgamma agonists may promote colon cancer under certain circumstances. This possibility warrants considerable attention since several million individuals with type II diabetes are currently taking PPARgamma agonists. This review will focus on recent data related to four critical questions: what is the physiological function of PPARgamma in gastrointestinal epithelial cells; how does PPARgamma suppress colon carcinogenesis; is PPARgamma a tumor promoter; and what is the future of PPARgamma in colon cancer prevention?