Impairment of skin wound healing in β-1,4-galactosyltransferase-deficient mice with reduced leukocyte recruitment
Impairment of skin wound healing in β-1,4-galactosyltransferase-deficient mice with reduced leukocyte recruitment
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DOI：
10.1016/s0002-9440(10)63217-8
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发表时间：
2004-04-01
影响因子：
6
通讯作者：
Asano, M
中科院分区：
文献类型：
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作者：
Mori, R;Kondo, T;Asano, M
已知细胞表面碳水化合物链有助于细胞迁移、相互作用和增殖，但它们在皮肤伤口愈合中的作用尚未得到评估。我们利用缺乏β-1，4-半乳糖基转移酶-I(Beta4GalT-I)的突变小鼠，研究了β4-半乳糖化碳水化合物链在皮肤伤口愈合中的生物学作用。β-1，4-半乳糖基转移酶-I负责N-糖链中2型链和O-糖链中核心2分支的生物合成。与对照小鼠相比，Beta4GalT-I基因缺陷小鼠的伤口愈合显著延迟，再上皮化、胶原合成和血管生成减少。这些小鼠伤口部位的中性粒细胞和巨噬细胞募集也受到损害，可能是由于选择素配体缺乏所致。与白细胞浸润减少相对应，β4GalT-I-/-小鼠巨噬细胞源性趋化因子、转化生长因子-β1和血管内皮生长因子的表达水平均降低。这些结果表明，β4-半乳糖化糖链在皮肤创面愈合中起关键作用，它通过调节白细胞的渗透和表皮细胞的生长，从而影响趋化因子和生长因子的产生。本研究介绍了一种适合研究皮肤创伤愈合分子机制的小鼠模型，并首次报道了碳水化合物对皮肤创伤愈合有很强的影响。
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-galactosyl-transferase-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 have a strong influence on skin wound healing.