Comparison of mucosal absorption-enhancing activity between a claudin-3/-4 binder and a broadly specific claudin binder.
Comparison of mucosal absorption-enhancing activity between a claudin-3/-4 binder and a broadly specific claudin binder.
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DOI：
10.1016/j.bbrc.2012.05.060
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发表时间：
2012-06
影响因子：
3.1
通讯作者：
Koji Matsuhisa;M. Kondoh;Hidehiko Suzuki;K. Yagi
中科院分区：
文献类型：
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作者：
Koji Matsuhisa;M. Kondoh;Hidehiko Suzuki;K. Yagi
相邻粘膜上皮细胞之间的细胞间隙由紧密连接（TJ）密封，防止溶质自由移动穿过上皮。紧密连接蛋白（Claudins，CLs）是一个由27个膜蛋白组成的家族，是TJ海豹的重要组成部分.我们先前使用CL-3/-4结合剂，即产气荚膜梭菌肠毒素（C-CPE）的C-末端片段，以表明CL调节是一种有前途的增强粘膜吸收的方法。最近，通过使用C-CPE突变体库，我们开发了对CL-1、-2、-4和-5具有广泛特异性的CL结合剂（m19）。在这里，我们比较了C-CPE和m19的粘膜吸收增强活性。两种CL结合剂均能促进分子量为4000和150，000 Da的右旋糖酐在大鼠空肠的吸收，促进分子量为4000 Da的右旋糖酐在大鼠鼻腔的吸收，但对分子量为150，000 Da的右旋糖酐的吸收无明显影响。虽然两种粘合剂显示出相似的右旋糖酐（4000 Da）的鼻吸收促进活性，但m19表现出比C-CPE更有效的空肠吸收促进作用。这些结果表明，粘膜吸收增强活性可能会修改调制CL的特异性。
Intercellular spaces between adjacent mucosal epithelial cells are sealed by tight junctions (TJs) that prevent the free movement of solutes across the epithelium. Claudins (CLs), a family of 27 integral membrane proteins, are essential components for TJ seals. We previously used a CL-3/-4 binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), to show that CL modulation is a promising method to enhance mucosal absorption. Recently, by using a C-CPE mutant library, we developed a CL binder (m19) with broad specificity to CL-1, -2, -4, and -5. Here, we compared the mucosal absorption-enhancing activity of C-CPE and m19. Both CL binders enhanced jejunal absorption of dextran with a molecular mass of 4000 and 150,000Da and nasal absorption of dextran with a mass of 4000Da but not 150,000Da in rats. Although both binders showed similar nasal absorption-enhancing activity of dextran (4000Da), m19 exhibited a more potent jejunal absorption-enhancing effect than that of C-CPE. These findings suggest that mucosal absorption-enhancing activity may be modified by modulating CL specificity.