Premium
Sphingomyelin maintains the cutaneous barrier via regulation of the STAT3 pathway
Author(s) -
Komuro Mariko,
Nagane Masaki,
Fukuyama Tomoki,
Luo Xiaolin,
Hiraki Shinobu,
Miyanabe Masakatsu,
Ishikawa Miyuki,
Niwa Chiaki,
Murakami Hironobu,
Okamoto Mariko,
Yamashita Tadashi
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100721rr
Subject(s) - stat3 , stat protein , signal transduction , sphingolipid , phosphorylation , sphingomyelin , hippo signaling pathway , cancer research , activator (genetics) , janus kinase , downregulation and upregulation , microbiology and biotechnology , biology , chemistry , medicine , endocrinology , receptor , biochemistry , cholesterol , gene
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.