Kurasawa Masumi, Kuroda Shohei, Kida Naoko, Murata Michiyo, Oba Ai, Yamamoto Takuya, Sasaki Hiroyuki
Pola Chemical Industries Inc., 560 Kashio-cho, Totsuka-ku, Yokohama 244-0812, Japan.
Biochem Biophys Res Commun. 2009 Apr 3;381(2):171-5. doi: 10.1016/j.bbrc.2009.02.005. Epub 2009 Feb 10.
Tight junctions (TJs) restrict paracellular flux of water and solutes in epithelia and endothelia. In epidermis, the physiological role of TJs is not fully understood. In this study, sodium caprate (C10), which dilates intestinal TJs, was applied to cultured human epidermal keratinocytes and reconstructed human epidermis to investigate the effects of C10 on epidermal TJs. C10 treatment decreased transepithelial electrical resistance and increased paracellular permeability, although Western blots showed that the expression of TJ-related transmembrane proteins was not decreased. The effects of C10 were reversible. Immunofluorescence microscopy and immuno-replica electron microscopy showed that the localization of TJ strands were disintegrated, concomitant with the dispersion and/or disappearance of TJ-related molecules from the cell surface. These findings suggest that C10 impairs barrier function by physically disrupting TJ conformation in the epidermis. Furthermore, these results also show that proper localization of the molecules on the cellular membrane is important for TJ barrier function.
紧密连接（TJs）限制上皮细胞和内皮细胞中水和溶质的细胞旁通量。在表皮中，紧密连接的生理作用尚未完全了解。在本研究中，将可扩张肠道紧密连接的癸酸钠（C10）应用于培养的人表皮角质形成细胞和重建的人表皮，以研究C10对表皮紧密连接的影响。尽管蛋白质免疫印迹显示紧密连接相关跨膜蛋白的表达未降低，但C10处理降低了跨上皮电阻并增加了细胞旁通透性。C10的作用是可逆的。免疫荧光显微镜和免疫复型电子显微镜显示，紧密连接链的定位被破坏，同时紧密连接相关分子从细胞表面分散和/或消失。这些发现表明，C10通过物理破坏表皮中的紧密连接构象来损害屏障功能。此外，这些结果还表明，分子在细胞膜上的正确定位对于紧密连接屏障功能很重要。
