H Antigen expression modulates epidermal Keratinocyte Integrity and differentiation

被引:2
|
作者
Jin, Seon-Pil [1 ,2 ,3 ]
Oh, Jang-Hee [1 ,2 ]
Kim, Namjoo Kaylee [1 ,2 ]
Chung, Jin Ho [1 ,2 ,3 ]
机构
[1] Seoul Natl Univ Hosp, Dept Dermatol, Seoul, South Korea
[2] Seoul Natl Univ, Inst Human Environm Interface Biol, Med Res Ctr, Seoul, South Korea
[3] Seoul Natl Univ, Coll Med, Dept Dermatol, Seoul, South Korea
关键词
Blood group antigen; fucosyltransferase1; FUT1; Cell-cell adhesion; Desmosome; Glycosylation; Desmoglein; Epidermal growth factor receptor; EGFR; BLOOD-GROUP ANTIGENS; DESMOSOME; SUPPRESSION; DESMOGLEIN; FUT1; SKIN; RESISTANCE; ADHESIVE; STRENGTH; NUMBER;
D O I
10.1186/s40659-024-00541-x
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
BackgroundABO 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.MethodPrimary human keratinocytes were transfected with FUT1 siRNA or recombinant adenovirus for FUT1 overexpression. Cell adhesion and desmosome characteristics and their underlying mechanisms were analyzed.ResultThe 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.ConclusionThe 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.
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页数:13
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