Sphingomyelin maintains the cutaneous barrier via regulation of the STAT3 pathway
Sphingomyelin maintains the cutaneous barrier via regulation of the STAT3 pathway
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DOI：
10.1096/fj.202100721rr
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发表时间：
2022-04-01
期刊：
影响因子：
4.8
通讯作者：
Yamashita, Tadashi
中科院分区：
文献类型：
--
作者：
Komuro, Mariko;Nagane, Masaki;Yamashita, Tadashi
表皮组织在维持内环境稳定和防止皮肤屏障失调方面起着至关重要的作用。鞘磷脂(SM)是由鞘磷脂合成酶(SMS)1和2合成的一种鞘磷脂，通过调节脂筏功能参与信号转导。虽然已经报道了短信对炎症性疾病的影响，但它在皮炎中的作用还没有得到澄清。在这项研究中，我们利用SGMS1和SGMS2缺陷小鼠建立的皮炎模型，研究了SM在皮肤屏障中的作用。SM缺乏可损害皮肤炎症，上调上皮组织中信号转导和转录激活子3(STAT3)的磷酸化。此外，利用小鼠胚胎成纤维细胞，在SGMS缺陷的细胞中，STAT3对IL-6刺激的敏感性增加。使用临床JAK抑制剂tofacitinib，研究表明SM缺乏可能通过JAK激活参与STAT3的磷酸化。总体而言，这些结果表明SM是通过STAT3途径维持皮肤屏障所必需的，这表明SM可能是皮炎治疗的潜在治疗靶点。
Epidermal tissues play vital roles in maintaining homeostasis and preventing the dysregulation of the cutaneous barrier. Sphingomyelin (SM), a sphingolipid synthesized by sphingomyelin synthase (SMS) 1 and 2, is involved in signal transduction via modulation of lipid-raft functions. Though the implications of SMS on inflammatory diseases have been reported, its role in dermatitis has not been clarified. In this study, we investigated the role of SM in the cutaneous barrier using a dermatitis model established by employing Sgms1 and 2 deficient mice. SM deficiency impaired the cutaneous inflammation and upregulated signal transducer and activator of transcription 3 (STAT3) phosphorylation in epithelial tissues. Furthermore, using mouse embryonic fibroblast cells, the sensitivity of STAT3 to Interleukin-6 stimulation was increased in Sgms-deficient cells. Using tofacitinib, a clinical JAK inhibitor, the study showed that SM deficiency might participate in STAT3 phosphorylation via JAK activation. Overall, these results demonstrate that SM is essential for maintaining the cutaneous barrier via the STAT3 pathway, suggesting SM could be a potential therapeutic target for dermatitis treatment.