Matrix metalloproteinases (MMPs) are required for re-epithelialization of cutaneous wounds
Matrix metalloproteinases (MMPs) are required for re-epithelialization of cutaneous wounds
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DOI：
10.1007/s004030050459
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发表时间：
1999-11-01
影响因子：
3
通讯作者：
Ågren, MS
中科院分区：
文献类型：
--
作者：
Ågren, MS
基质金属蛋白酶（MMPs）是中性锌依赖性内肽酶，对大多数细胞外基质分子具有底物特异性。MMPs参与生理和病理生物学过程。在伤口修复中，一些MMPs在迁移上皮中上调，尽管其存在的生物学意义尚不清楚。为了阐明MMPs在皮肤创面上皮迁移中的作用，将广谱合成MMP抑制剂（GM 6001, 10 mg/ml）局部应用于家猪部分厚度创面以抑制内源性MMPs，经高效液相色谱法测定，经处理的猪创面液中GM 6001的溶解浓度为0.06 mg/ml （150 μ M）。酶谱分析表明，在这个浓度下溶解的GM 6001几乎完全消除了伤口液中存在的所有酶活性。形态学评估显示，治疗66小时后，GM 6001处理的伤口上皮覆盖率（50.0 +/- 29.6%，平均+/- SD， n = 6）与单独使用载体（水凝胶）处理的伤口（87.4 +/- 10.6%,n = 6）相比显著降低（P = 0.002）。外用GM 6001不影响皮肤炎症细胞浸润的程度，也不影响5-溴-2'-脱氧尿苷（一种衡量伤口上皮细胞增殖的指标）的体内掺入，这表明GM 6001减少的再上皮化不是由于干扰炎症反应或上皮细胞增殖造成的。我们的研究结果表明MMPs直接参与了湿润皮肤伤口上皮细胞的重铺。
Matrix metalloproteinases (MMPs) are neutral zinc-dependent endopeptidases with substrate specificity for most extracellular matrix molecules. MMPs participate in physiological and pathological biological processes. In wound repair, several MMPs are upregulated in migrating epithelium although the biological significance of their presence is unknown. To elucidate the role of MMPs in epithelial migration of cutaneous wounds, a broad-spectrum synthetic MMP inhibitor (GM 6001, 10 mg/ml) was applied topically to partial-thickness wounds in domestic pigs to inhibit endogenous MMPs, The concentration of solubilized GM 6001 in wound fluid obtained from treated porcine wounds was 0.06 mg/ml (150 mu M) as determined by high-performance liquid chromatography, Zymographic analysis showed that GM 6001 solubilized at this concentration abolished almost completely all enzymatic activity present in wound fluid. Epithelial coverage, assessed morphometrically, after 66 h of treatment was significantly decreased (P = 0.002) in GM 6001-treated wounds (50.0 +/- 29.6%, mean +/- SD, n = 6) compared with wounds treated with the vehicle (a hydrogel) alone (87.4 +/- 10.6%, n = 6), Topical GM 6001 did not influence the degree of dermal inflammatory cell infiltrate or the in vivo incorporation of 5-bromo-2'-deoxyuridine las a measure of epithelial proliferation in the wounds) indicating that the reduced re-epithelialization with GM 6001 was not due to interference with the inflammatory response or epithelial proliferation, Our results suggest that MMPs are directly involved and necessary in epithelial resurfacing of moist skin wounds.