Finsen Laboratory, Copenhagen University Hospital, Copenhagen Biocenter, Ole Maaløes Vej 5, Copenhagen N, Denmark.
Exp Dermatol. 2010 Aug;19(8):e234-40. doi: 10.1111/j.1600-0625.2009.01062.x.
During healing of incisional skin wounds, migrating keratinocytes dissect their way under the crust to re-epithelialize the wounded area. The efficiency of this tissue remodelling process depends on the concomitant activity of several extracellular proteases, including members of the plasminogen activation (PA) system and the matrix metalloproteinase (MMP) family. Treatment with the broad spectrum MMP inhibitor, galardin, delays wound healing in wildtype mice and completely arrest wound healing in plasminogen (Plg)-deficient mice, indicating a functional overlap between plasmin- and galardin-sensitive MMPs during wound healing. To address whether MMP2 is accountable for the galardin-induced healing deficiency in wildtype and Plg-deficient mice, incisional skin wounds were generated in MMP2 single-deficient mice and in MMP2/Plg double-deficient mice and followed until healed. Alternatively, tissue was isolated 7 days post wounding for histological and biochemical analyses. No difference was found in the time from wounding to overt gross restoration of the epidermal surface between MMP2-deficient and wildtype control littermate mice. MMP2/Plg double-deficient mice were viable and fertile, and displayed an unchallenged general phenotype resembling that of Plg-deficient mice, including development of rectal prolapses. MMP2/Plg double-deficient mice displayed a slight increase in the wound length throughout the healing period compared with Plg-deficient mice. However, the overall time to complete healing was not significantly different between Plg-deficient and MMP2/Plg double-deficient mice. These results show that MMP2 activity is not essential for wound healing and indicate that lack of MMP2 only marginally potentiates the effect of Plg deficiency.
在切口皮肤伤口愈合过程中，迁移的角质形成细胞在痂下解剖，以重新上皮化受伤区域。这个组织重塑过程的效率取决于几种细胞外蛋白酶的协同活性，包括纤溶酶原激活（PA）系统和基质金属蛋白酶（MMP）家族的成员。广谱 MMP 抑制剂 galardin 的治疗会延迟野生型小鼠的伤口愈合，并完全阻止纤溶酶原（Plg）缺陷型小鼠的伤口愈合，表明纤溶酶和 galardin 敏感的 MMPs 在伤口愈合过程中存在功能重叠。为了确定 MMP2 是否对野生型和 Plg 缺陷型小鼠的 galardin 诱导的愈合缺陷负责，在 MMP2 单缺陷型小鼠和 MMP2/Plg 双缺陷型小鼠中生成切口皮肤伤口，并一直跟踪至愈合。或者，在创伤后 7 天分离组织进行组织学和生化分析。在 MMP2 缺陷型和野生型对照同窝仔鼠之间，从创伤到表皮表面明显恢复的时间没有差异。MMP2/Plg 双缺陷型小鼠具有活力和生育能力，并且表现出与 Plg 缺陷型小鼠相似的未受挑战的一般表型，包括直肠脱垂的发生。与 Plg 缺陷型小鼠相比，MMP2/Plg 双缺陷型小鼠在整个愈合期间的伤口长度略有增加。然而，Plg 缺陷型和 MMP2/Plg 双缺陷型小鼠之间完全愈合的总时间没有显著差异。这些结果表明 MMP2 活性对于伤口愈合不是必需的，并表明缺乏 MMP2 仅略微增强 Plg 缺陷的作用。
