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(American Journal of Pathology. 2004;164:1303-1314.)
© 2004 American Society for Investigative Pathology

Impairment of Skin Wound Healing in ß-1,4-Galactosyltransferase-Deficient Mice with Reduced Leukocyte Recruitment

Ryoichi Mori*, Toshikazu Kondo*{dagger}, Toshikazu Nishie{ddagger}, Tohru Ohshima* and Masahide Asano{ddagger}

From the Department of Forensic and Social Environmental Medicine,* Graduate School of Medical Science, and the Division of Transgenic Animal Science,{ddagger} Advanced Science Research Center, Kanazawa University, Kanazawa; and the Department of Legal Medicine,{dagger} Wakayama Medical University, Wakayama, Japan

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 ß4-galactosylated carbohydrate chains in skin wound healing using mutant mice that lack ß-1,4-galactosyltransferase-I (ß4GalT-I), which is responsible for the biosynthesis of the type 2 chain in N-glycans and the core 2 branch in O-glycans. ß4GalT-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-ß1, and vascular endothelial growth factor were all reduced in ß4GalT-I-/- mice. These results demonstrate that ß4-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.





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