Kubo Terufumi, Sugimoto Kotaro, Kojima Takashi, Sawada Norimasa, Sato Noriyuki, Ichimiya Shingo
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):205-11. doi: 10.1016/j.bbrc.2014.10.148. Epub 2014 Nov 4.
In the epidermis, tight junction (TJ) structure is specifically located in the stratum granulosum, where the expression of ΔNp63, a p53 family transcription factor, is attenuated. Since the relationship between ΔNp63 and barrier function has not been fully uncovered, we assessed expression profiles of TJ proteins in skin tissues and cultured keratinocytes. The results showed that expression of ΔNp63 and that of claudin-4 were inversely correlated in healthy human epidermis. In vitro studies using HaCaT keratinocytes revealed functional relevance of ΔNp63 and claudin-4. Curiously, Toll-like receptor (TLR)-3 ligand, which is known to be liberated from damaged cells, suppressed ΔNp63 expression and concomitantly upregulated claudin-4 expression in primary keratinocytes. More interestingly, a broad expression pattern of claudin-4 was found in the epidermis of atopic dermatitis (AD), a barrier defect disorder, which contains ΔNp63-lacking keratinocytes as we reported previously. Therefore, upregulation of claudin-4 expression regulated by ΔNp63 might be associated with complementary or repair responses of damaged keratinocytes with AD.
在表皮中，紧密连接（TJ）结构特异性地位于颗粒层，在该层中，p53家族转录因子ΔNp63的表达减弱。由于ΔNp63与屏障功能之间的关系尚未完全阐明，我们评估了皮肤组织和培养的角质形成细胞中TJ蛋白的表达谱。结果显示，在健康人表皮中，ΔNp63的表达与claudin-4的表达呈负相关。使用HaCaT角质形成细胞进行的体外研究揭示了ΔNp63与claudin-4的功能相关性。奇怪的是，已知从受损细胞中释放的Toll样受体（TLR）-3配体在原代角质形成细胞中抑制了ΔNp63的表达，并同时上调了claudin-4的表达。更有趣的是，在特应性皮炎（AD）（一种屏障缺陷性疾病）的表皮中发现了claudin-4的广泛表达模式，如我们之前报道的，该表皮含有缺乏ΔNp63的角质形成细胞。因此，由ΔNp63调节的claudin-4表达上调可能与AD中受损角质形成细胞的互补或修复反应有关。
