H Antigen expression modulates epidermal Keratinocyte Integrity and differentiation.
Humans
Keratinocytes
/ metabolism
Cell Differentiation
/ physiology
Fucosyltransferases
/ genetics
Desmosomes
/ metabolism
Cells, Cultured
Cell Adhesion
/ physiology
ErbB Receptors
/ metabolism
ABO Blood-Group System
/ genetics
Galactoside 2-alpha-L-fucosyltransferase
RNA, Small Interfering
/ genetics
Blood group antigen
Cell-cell adhesion
Desmoglein
Desmosome
EGFR
Epidermal growth factor receptor
FUT1
Glycosylation
fucosyltransferase1
Journal
Biological research
ISSN: 0717-6287
Titre abrégé: Biol Res
Pays: England
ID NLM: 9308271
Informations de publication
Date de publication:
18 Oct 2024
18 Oct 2024
Historique:
received:
17
04
2024
accepted:
26
08
2024
medline:
18
10
2024
pubmed:
18
10
2024
entrez:
18
10
2024
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHOD
METHODS
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.
RESULT
RESULTS
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.
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 39420441
doi: 10.1186/s40659-024-00541-x
pii: 10.1186/s40659-024-00541-x
doi:
Substances chimiques
Fucosyltransferases
EC 2.4.1.-
ErbB Receptors
EC 2.7.10.1
ABO Blood-Group System
0
Galactoside 2-alpha-L-fucosyltransferase
EC 2.4.1.69
RNA, Small Interfering
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
72Subventions
Organisme : Phase III (Postdoctoral fellowship) grant of the SPST (SNU-SNUH Physician Scientist Training) Program
ID : Phase III (Postdoctoral fellowship) grant of the SPST (SNU-SNUH Physician Scientist Training) Program
Organisme : Seoul National University Hospital
ID : 1920230010
Organisme : Ministry of Science and ICT, South Korea
ID : 2019M3A9I3091696
Informations de copyright
© 2024. The Author(s).
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