Sokabe Takaaki, Tominaga Makoto
Division of Cell Signaling; Okazaki Institute for Integrative Bioscience; National Institutes of Natural Sciences.
Commun Integr Biol. 2010 Nov;3(6):619-21. doi: 10.4161/cib.3.6.13461. Epub 2010 Nov 1.
The skin barrier function is indispensable for terrestrial animals to avoid dehydration. The function is achieved by a hydrophobic cornified layer consisting of dead keratinocytes and lipids, and by an intercellular junction barrier formed among differentiated keratinocytes. A recent report demonstrated that TRPV4, one of the temperature-sensitive cation channels, contributes to the formation and maintenance of the intercellular junction-dependent barrier in the skin. TRPV4 associates with the E-cadherin complex via β-catenin, and thereby participates in the promotion of cell-cell junction development. TRPV4 allows influx of Ca(2+) ions from the extracellular space at physiological skin temperatures. The Ca(2+) influx induces Rho activation and promotes actin fiber organization and junction formation, thereby augmenting barrier integrity. Indeed, the intercellular junction structures and the skin barrier function were impaired in TRPV4-deficeint mice. This novel role of TRPV4 in keratinocytes may explain the significant correlation between temperature and the condition of skin.>
皮肤屏障功能对于陆生动物避免脱水至关重要。该功能通过由死亡角质形成细胞和脂质组成的疏水性角质层以及分化的角质形成细胞之间形成的细胞间连接屏障来实现。最近的一份报告表明，温度敏感阳离子通道之一的TRPV4有助于皮肤中细胞间连接依赖性屏障的形成和维持。TRPV4通过β-连环蛋白与E-钙黏蛋白复合物结合，从而参与促进细胞间连接的发育。在生理皮肤温度下，TRPV4允许Ca(2+)离子从细胞外空间流入。Ca(2+)内流诱导Rho激活并促进肌动蛋白纤维组织和连接形成，从而增强屏障完整性。事实上，TRPV4缺陷小鼠的细胞间连接结构和皮肤屏障功能受损。TRPV4在角质形成细胞中的这一新作用可能解释了温度与皮肤状况之间的显著相关性。
