Shiseido Innovative Science Research and Development Center, Yokohama, Japan.
J Invest Dermatol. 2012 Jan;132(1):69-75. doi: 10.1038/jid.2011.256. Epub 2011 Sep 1.
Ryanodine receptors (RyRs) have an important role as calcium channels in the regulation of intracellular calcium levels in the nervous system and muscle. In the present study, we investigated the expression of RyR in human epidermis. Immunohistochemical studies and reverse transcription-PCR indicated the expression of RyR type 1, 2, and 3 proteins in epidermal keratinocytes. The expression level of each RyR subtype was higher in differentiating keratinocytes than in proliferative cells. We also demonstrated the functional expression of RyR by calcium imaging. In cultured human keratinocytes, application of the RyR agonist 4-chloro-m-cresol (CMC) induced elevation of the intracellular calcium concentration, and co-application of the RyR antagonist 1,1'-diheptyl-4,4'-bipyridinium dibromide (DHBP) blocked the elevation. Application of CMC accelerated keratinocyte differentiation in vitro. On the other hand, topical application of CMC after tape-stripping of hairless mouse skin delayed barrier recovery, whereas application of an RyR antagonist, dantrolene or DHBP, accelerated the barrier recovery. These results suggest that RyR expressed in epidermal keratinocytes is associated with both differentiation of keratinocytes and epidermal barrier homeostasis.
Ryanodine 受体（RyRs）作为钙通道，在神经系统和肌肉细胞内钙离子水平的调节中具有重要作用。本研究调查了 RyR 在人表皮中的表达。免疫组织化学研究和反转录-PCR 表明 RyR 型 1、2 和 3 蛋白在表皮角质形成细胞中表达。每种 RyR 亚型的表达水平在分化的角质形成细胞中高于增殖细胞。我们还通过钙成像证明了 RyR 的功能表达。在培养的人角质形成细胞中，应用 RyR 激动剂 4-氯间甲酚（CMC）诱导细胞内钙离子浓度升高，而 RyR 拮抗剂 1,1'-二庚基-4,4'-联吡啶二溴化物（DHBP）的共同应用则阻断了这种升高。CMC 的应用加速了体外角质形成细胞的分化。另一方面，CMC 在无毛小鼠皮肤胶带剥离后的局部应用延迟了屏障的恢复，而 RyR 拮抗剂丹曲林或 DHBP 的应用则加速了屏障的恢复。这些结果表明，表皮角质形成细胞中表达的 RyR 与角质形成细胞的分化和表皮屏障的动态平衡有关。
