Impairment of skin wound healing in beta-1,4-galactosyltransferase-deficient mice with reduced leukocyte recruitment.
Cell-surface carbohydrate chains are known to contribute to cell migration, interactions, and proliferation, but their roles in skin wound healing have not been evaluated. We examined the biological roles of beta4-galactosylated carbohydrate chains in skin wound healing using mutant mice that lack beta-1,4-galactosyltransferase-I (beta4GalT-I), which is responsible for the biosynthesis of the type 2 chain in N-glycans and the core 2 branch in O-glycans. beta4GalT-I-deficient mice showed significantly delayed wound healing with reduced re-epithelialization, collagen synthesis, and angiogenesis, compared with control mice. Neutrophil and macrophage recruitment at wound sites was also impaired in these mice probably because of selectin-ligand deficiency. In accordance with the reduced leukocyte infiltration, the expression levels of macrophage-derived chemokines, transforming growth factor-beta1, and vascular endothelial growth factor were all reduced in beta4GalT-I(-/-) mice. These results demonstrate that beta4-galactosylated carbohydrate chains play a critical role in skin wound healing by mediating leukocyte infiltration and epidermal cell growth, which affects the production of chemokines and growth factors. This study introduces a suitable mouse model for investigating the molecular mechanisms of skin wound healing and is the first report showing that carbohydrate chains have a strong influence on skin wound healing.
Mori
Ryoichi
R
Department of Forensic and Social Environmental Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Kondo
Toshikazu
T
Nishie
Toshikazu
T
Ohshima
Tohru
T
Asano
Masahide
M
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D003094:Collagen / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009237:N-Acetyllactosamine Synthase / Q000172:deficiency*; D018919:Neovascularization, Physiologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014945:Wound Healing / Q000502:physiology*
D018925:Chemokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D009237:N-Acetyllactosamine Synthase