TY - JOUR
T1 - Barrier Abnormalities in Type 1 Diabetes Mellitus
T2 - The Roles of Inflammation and Ceramide Metabolism
AU - Shin, Kyong Oh
AU - Kim, Bokyung
AU - Choi, Yerim
AU - Bae, Yoo Jin
AU - Park, Jae Ho
AU - Park, Soo Hyun
AU - Hwang, Jin Taek
AU - Choi, Eung Ho
AU - Uchida, Yoshikazu
AU - Park, Kyungho
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/4
Y1 - 2024/4
N2 - Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation–mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.
AB - Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation–mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.
KW - Ceramide
KW - Diabetes mellitus
KW - Epidermal permeability barrier
KW - Inflammation
KW - Serine racemase
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U2 - 10.1016/j.jid.2023.10.010
DO - 10.1016/j.jid.2023.10.010
M3 - Article
C2 - 37952608
AN - SCOPUS:85180282785
SN - 0022-202X
VL - 144
SP - 802-810.e5
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -