Department of Dermatology, Seoul National University Hospital, Seoul, Republic of Korea.
Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Biol Res. 2024 Oct 18;57(1):72. doi: 10.1186/s40659-024-00541-x.
ABO blood group antigens (ABH antigens) are carbohydrate chains glycosylated on epithelial and red blood cells. Recent findings suggest reduced ABH expression in psoriasis and atopic dermatitis, a chronic inflammatory skin disease with retained scale. H antigen, a precursor for A and B antigens, is synthesized by fucosyltransferase 1 (FUT1). Desmosomes, critical for skin integrity, are known to require N-glycosylation for stability. We investigate the impact of H antigens, a specific type of glycosylation, on desmosomes in keratinocytes.
Primary human keratinocytes were transfected with FUT1 siRNA or recombinant adenovirus for FUT1 overexpression. Cell adhesion and desmosome characteristics and their underlying mechanisms were analyzed.
The knockdown of FUT1, responsible for H2 antigen expression in the skin, increased cell-cell adhesive strength and desmosome size in primary cultured keratinocytes without altering the overall desmosome structure. Desmosomal proteins, including desmogleins or plakophilin, were upregulated, suggesting enhanced desmosome assembly. Reduced H2 antigen expression via FUT1 knockdown led to increased keratinocyte differentiation, evidenced by elevated expression of differentiation markers. Epidermal growth factor receptor (EGFR) has been described to be associated with FUT1 and promotes cell migration and differentiation. The effects of FUT1 knockdown were recapitulated by an EGFR inhibitor concerning desmosomal proteins and cellular differentiation. Further investigation demonstrated that the FUT1 knockdown reduced EGFR signaling by lowering the levels of EGF ligands rather than directly regulating EGFR activity. Moreover, FUT1 overexpression reversed the effects observed in FUT1 knockdown, resulting in the downregulation of desmosomal proteins and differentiation markers while increasing both mRNA and protein levels of EGFR ligands.
The expression level of FUT1 in the epidermis appears to influence cell-cell adhesion and keratinocyte differentiation status, at least partly through regulation of H2 antigen and EGFR ligand expression. These observations imply that the fucosylation of the H2 antigen by FUT1 could play a significant role in maintaining the molecular composition and regulation of desmosomes and suggest a possible involvement of the altered H2 antigen expression in skin diseases, such as psoriasis and atopic dermatitis.
ABO 血型抗原（ABH 抗原）是糖基化在上皮细胞和红细胞上的碳水化合物链。最近的研究结果表明，银屑病和特应性皮炎（一种慢性炎症性皮肤病，保留鳞屑）中 ABH 表达减少。H 抗原是 A 和 B 抗原的前体，由岩藻糖基转移酶 1（FUT1）合成。已知参与皮肤完整性的桥粒需要 N-糖基化才能稳定。我们研究了 H 抗原（一种特定类型的糖基化）对角质形成细胞中桥粒的影响。
用 FUT1 siRNA 或重组腺病毒转染原代人角质形成细胞以过表达 FUT1。分析细胞黏附和桥粒的特征及其潜在机制。
负责皮肤中 H2 抗原表达的 FUT1 敲低增加了原代培养角质形成细胞的细胞间黏附力和桥粒大小，而不改变整体桥粒结构。桥粒蛋白，包括桥粒糖蛋白或桥粒斑蛋白，上调，表明桥粒组装增强。通过 FUT1 敲低降低 H2 抗原表达导致角质形成细胞分化增加，证据是分化标志物的表达升高。表皮生长因子受体（EGFR）已被描述与 FUT1 相关，并促进细胞迁移和分化。FUT1 敲低对 EGFR 抑制剂的影响涉及桥粒蛋白和细胞分化。进一步的研究表明，FUT1 敲低通过降低 EGF 配体的水平而不是直接调节 EGFR 活性来降低 EGFR 信号。此外，FUT1 过表达逆转了 FUT1 敲低观察到的效果，导致桥粒蛋白和分化标志物的下调，同时增加 EGFR 配体的 mRNA 和蛋白水平。
表皮中 FUT1 的表达水平似乎影响细胞间黏附和角质形成细胞分化状态，至少部分通过调节 H2 抗原和 EGFR 配体的表达。这些观察结果表明，FUT1 对 H2 抗原的岩藻糖基化可能在维持桥粒的分子组成和调节中发挥重要作用，并提示皮肤疾病（如银屑病和特应性皮炎）中 H2 抗原表达的改变可能参与其中。
