Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Curr Med Chem. 2011;18(12):1861-5. doi: 10.2174/092986711795496809.
Tight junctions (TJs) play pivotal roles in the fence and barrier functions of epithelial and endothelial cell sheets. Since the 1980s, the modulation of the TJ barrier has been utilized as a method for drug absorption. Over the last decade, the structural and functional biochemical components of TJs, such as occludin and claudin, have been determined, providing new insights into TJ-based pharmaceutical therapy. For example, the modulation of the claudin barrier enhances the jejunal absorption of drugs, and claudin expression is deregulated in cancer cells. Claudin is a co-receptor for the hepatitis C virus. Moreover, claudin is modulated during inflammatory conditions. These findings indicate that claudins are promising drug targets. In this review, we discuss the seeds of claudin-based drug development, which may provide potential pharmaceutical breakthroughs in the future.
紧密连接(TJs)在上皮细胞和内皮细胞片的篱笆和障碍功能中起着关键作用。自 20 世纪 80 年代以来,TJ 屏障的调节已被用作药物吸收的一种方法。在过去的十年中,TJ 的结构和功能生化成分,如闭合蛋白和紧密连接蛋白,已经被确定,为基于 TJ 的药物治疗提供了新的见解。例如,紧密连接蛋白屏障的调节增强了药物在空肠中的吸收,并且在癌细胞中紧密连接蛋白的表达失调。紧密连接蛋白是丙型肝炎病毒的共受体。此外,在炎症条件下,紧密连接蛋白也会发生调节。这些发现表明紧密连接蛋白是有前途的药物靶点。在这篇综述中,我们讨论了基于紧密连接蛋白的药物开发的种子,这可能为未来提供潜在的药物突破。