Shimizu Yoshimi, Nagase Shotaro, Yagi Kiyohito, Kondoh Masuo
Graduate School of Pharmaceutical Sciences, Osaka University.
Yakugaku Zasshi. 2014;134(5):641-5. doi: 10.1248/yakushi.14-00006-5.
Epithelium plays pivotal roles in biological barrier separating the inside of body and the outside environment. Ninety percent of malignant tumors are derived from epithelium. Most pathological microorganisms invade into the body from mucosal epithelium. Thus, epithelium is potential targets for drug development. Claudins (CLs), a family of tetra-transmembrane protein consisting of over 20 members, are structural and functional components of tight junction-seals in epithelium. Modulation of CL-seals enhanced mucosal absorption of drugs. CLs are often over-expressed in malignant tumors. CL-4 expression is increased in the epithelial cells covering the mucosal immune tissues. Very recently, CLs are also expected to be targets for traumatic brain injury and regenerative therapy. In this review, we overview the past, the present and the future of CLs-targeted drug development.
上皮组织在分隔身体内部与外部环境的生物屏障中发挥着关键作用。90%的恶性肿瘤起源于上皮组织。大多数致病微生物从黏膜上皮侵入人体。因此,上皮组织是药物研发的潜在靶点。紧密连接蛋白(CLs)是一个由20多个成员组成的四跨膜蛋白家族,是上皮组织中紧密连接密封的结构和功能成分。调节紧密连接蛋白密封可增强药物的黏膜吸收。紧密连接蛋白在恶性肿瘤中常过度表达。覆盖黏膜免疫组织的上皮细胞中紧密连接蛋白4的表达增加。最近,紧密连接蛋白也有望成为创伤性脑损伤和再生治疗的靶点。在本综述中,我们概述了以紧密连接蛋白为靶点的药物研发的过去、现在和未来。