Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase2 and-9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing
Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase2 and-9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing
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DOI：
10.1111/j.1067-1927.2004.012314.x
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发表时间：
2004-05-01
影响因子：
2.9
通讯作者：
Brown, NJ
中科院分区：
文献类型：
--
作者：
Gillard, JA;Reed, MWR;Brown, NJ
蛋白水解活性是创伤愈合过程中细胞外基质周转所必需的。基质金属蛋白酶可以共同切割细胞外基质的所有组分，内源性组织金属蛋白酶抑制剂-1调节其活性。在不同术后时间（n = 92）或手术期间采集的乳腺组织（对照，n = 17），用于研究人伤口愈合过程中基质金属蛋白酶-2和-9以及金属蛋白酶-1的组织抑制剂的时间和空间活性。基质金属蛋白酶活性，使用淬灭荧光底物测定法测定，与对照相比，在早期愈合期间（3-8周）增加，然后在手术后24 - 36周之间降低（p < 0.05，直到24周，Mann-Whitney U检验）。基质金属蛋白酶-9表达的免疫组化评分显着升高，与对照组相比，瘢痕内皮细胞和成纤维细胞从2至12和20周，分别。基质金属蛋白酶-2染色仅在成纤维细胞中观察到，在手术后8-12周达到最高水平，减少了1.5年，但仍显着增加。金属蛋白酶组织抑制剂-1染色相对稀疏，但在术后8周显著增加。这些结果表明，基质金属蛋白酶是目前在伤口愈合早期，当血管生成的水平升高，并表明，基质金属蛋白酶-9可能发挥重要作用。基质金属蛋白酶-2和-9在成纤维细胞中的后期表达表明在细胞外基质重塑中的作用。
Proteolytic activity is required for the turnover of the extracellular matrix during wound healing. Matrix metalloproteinases can collectively cleave all components of the extracellular matrix, with the endogenous tissue inhibitor of metalloproteinase-1 regulating their activity. Breast tissue taken at varying postoperative times (n = 92) or during surgery (controls, n = 17), was used to investigate the temporal and spatial activity of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human wound healing, Matrix metalloproteinase activity, determined using a quenched fluorescence substrate assay, increased during early healing (3-8 weeks) compared to controls, and then decreased between 24 and 36 weeks after surgery (p < 0.05 until 24 weeks, Mann-Whitney U-test). Immunohistochemistry scores for matrix metalloproteinase-9 expression were significantly elevated compared to controls in scar endothelial cells and fibroblasts from 2 until 12 and 20 weeks, respectively. Matrix metalloproteinase-2 staining was observed exclusively in fibroblasts, reaching maximum levels 8-12 weeks after surgery, decreasing by 1.5 years but remaining significantly increased. Tissue inhibitor of metalloproteinase-1 staining was relatively sparse but was significantly increased until 8 weeks after surgery. These results show that matrix metalloproteinases are present at elevated levels during early wound healing, when angiogenesis occurs, and suggest that matrix metalloproteinase-9 may play a significant role. The later expression of matrix metalloproteinase-2 and -9 in fibroblasts suggests a role in extracellular matrix remodeling.