CaMKII regulates the strength of the epithelial barrier.
CaMKII regulates the strength of the epithelial barrier.
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DOI：
10.1038/srep13262
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发表时间：
2015-08-18
影响因子：
4.6
通讯作者：
Ikenouchi J
中科院分区：
文献类型：
--
作者：
Shiomi R;Shigetomi K;Inai T;Sakai M;Ikenouchi J
上皮细胞通过构建扩散屏障来定义我们身体内外之间的边界。上皮细胞的紧密连接(TJ)作为屏障，阻止有害微生物入侵人体，阻止水或离子从体内自由扩散。因此，TJs的形成必须严格控制在上皮细胞中。然而，这种调控的分子机制在很大程度上是未知的。在本研究中，我们发现钙/钙调蛋白依赖的蛋白激酶II(CaMKII)是TJs屏障功能的调节因子。抑制CaMKII可导致TJ区扩大和屏障功能上调。抑制CaMKII诱导过量TJ的形成部分是通过激活AMP激活的蛋白激酶(AMPK)和随后的Claudin-1的磷酸化来实现的。由于上皮屏障的上调对于预防慢性炎症性疾病至关重要，确定CaMKII是TJ功能的调节因子，为开发治疗这些疾病的新药铺平了道路。
Epithelial cells define the boundary between the outside and the inside of our body by constructing the diffusion barrier. Tight junctions (TJs) of epithelial cells function as barriers against invasion of harmful microorganisms into the human body and free diffusion of water or ions from the body. Therefore, formation of TJs has to be strictly controlled in epithelial cells. However, the molecular mechanisms governing this regulation are largely unknown. In this study, we identified Ca2+/calmodulin-dependent protein kinase II (CaMKII) as a regulator of the barrier function of TJs. CaMKII inhibition led to enlargement of TJ-areas and up-regulation of the barrier function. CaMKII inhibition induced excess TJ formation in part by the activation of AMP-activated protein kinase (AMPK) and subsequent phosphorylation of claudin-1. As up-regulation of epithelial barriers is essential for the prevention of chronic inflammatory diseases, the identification of CaMKII as a modulator of TJ function paves the way for the development of new drugs to treat these diseases.