Elucidation of roles of gasotransmitters in the pathogenesis of atopic dermatitis

尽管有大量的报道表明，硫化氢与多种病理疾病和/或瘙痒有关，但还没有关于它参与角质形成细胞轴突引导分子表达的报道。我发现，硫化氢产生的酶在人皮肤(主要是角质形成细胞)中表达，在特应性皮炎(AD)皮损中表达增加。值得注意的是，硫化氢供体刺激上调了培养的正常人表皮角质形成细胞中NGF和ARTN的表达，下调了Sema3A的水平，这被认为是AD皮损外周瘙痒敏化的原因之一。我认为，在本工作所用的实验条件下，硫化氢的参与与AD有关。我们的数据提出了这样一种可能性，即硫化氢至少部分地通过改变KCs中的轴突引导分子来调节人类皮肤的表皮过度神经支配。这些发现增加了对气体递质在人类皮肤表皮超神经支配中的可能作用的洞察，特别是在皮肤发痒的炎症条件下，如AD。该项目的成果已发表在国际期刊《皮肤病科学杂志》上。

Despite the numerous reports that H2S is involved in various pathological diseases and/or itch, however, there have been no reports of its involvement in the expression of axon-guidance molecules in human keratinocytes (KCs).I found that H2S-producing enzymes were expressed in human skin (mainly KCs), and were increased in human atopic dermatitis (AD) skin lesion. Notably, the H2S donor stimulation upregulated NGF and ARTN, and downregulated Sema3A levels in the cultured normal human epidermal keratinocytes, which is considered to be a cause of peripheral itch sensitization in AD skin lesion. I suggest that the involvement of H2S under the experimental conditions used in the present work in relation with AD. Our data raise the possibility that H2S, at least in part, modulates the epidermal hyperinnervation of the human skin through alteration of axon-guidance molecules in KCs. These findings add insight of the possible role of gasotransmitter in epidermal hyperinnervation of human skin, especially in itchy skin inflammatory condition such as AD. The result of the project has been published in international journal (Journal of Dermatological Science).