Kojima Takashi, Kohno Takayuki, Kubo Terufumi, Kaneko Yakuto, Kakuki Takuya, Kakiuchi Akito, Kurose Makoto, Takano Ken-Ichi, Ogasawara Noriko, Obata Kazufumi, Nomura Kazuaki, Miyata Ryo, Konno Takumi, Ichimiya Shingo, Himi Tetsuo
Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Sapporo Medical University School of Medicine, Sapporo, Japan.
Ann N Y Acad Sci. 2017 Oct;1405(1):25-31. doi: 10.1111/nyas.13456. Epub 2017 Aug 30.
P63 is a regulator of cell-cell junction complexes in the epidermis. Claudin-4 is regulated via various factors in normal epithelial cells and diseases. We found that claudin-4 was directly regulated via p63 (TAp63 and ΔNp63) in human keratinocytes and nasal epithelial cells. In the epidermis of atopic dermatitis (AD), which contains ΔNp63-deficient keratinocytes, high expression of claudin-4 was observed. In primary keratinocytes, downregulation of ΔNp63 by treatment with short interfering RNA (siRNA)-p63 induced claudin-4 expression. In nasal epithelial cells in the context of rhinitis or nasal polyps, upregulation of TAp63 and downregulation of claudin-4 were observed. In primary nasal epithelial cells transfected with the human telomerase reverse transcriptase gene, knockdown of p63 by siRNAs induced claudin-4 expression. Taken together, these findings indicate that p63 is a negative regulator of claudin-4 expression. Understanding the regulation of claudin-4 via p63 in human epithelial cells may be important for developing therapies for allergies and drug delivery systems.
P63是表皮中细胞间连接复合体的一种调节因子。Claudin-4在正常上皮细胞和疾病中受多种因素调控。我们发现，在人角质形成细胞和鼻上皮细胞中，Claudin-4受p63（TAp63和ΔNp63）直接调控。在含有ΔNp63缺陷角质形成细胞的特应性皮炎（AD）表皮中，观察到Claudin-4高表达。在原代角质形成细胞中，用小干扰RNA（siRNA）-p63处理下调ΔNp63可诱导Claudin-4表达。在鼻炎或鼻息肉背景下的鼻上皮细胞中，观察到TAp63上调和Claudin-4下调。在用人类端粒酶逆转录酶基因转染的原代鼻上皮细胞中，siRNA敲低p63可诱导Claudin-4表达。综上所述，这些发现表明p63是Claudin-4表达的负调节因子。了解人上皮细胞中通过p63对Claudin-4的调控可能对开发过敏治疗方法和药物递送系统具有重要意义。
