MMP-13 Plays a Role in Keratinocyte Migration, Angiogenesis, and Contraction in Mouse Skin Wound Healing
MMP-13 Plays a Role in Keratinocyte Migration, Angiogenesis, and Contraction in Mouse Skin Wound Healing
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DOI：
10.2353/ajpath.2009.081080
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发表时间：
2009-08-01
影响因子：
6
通讯作者：
Okada, Yasunori
中科院分区：
文献类型：
--
作者：
Hattori, Noriko;Mochizuki, Satsuki;Okada, Yasunori
基质金属蛋白酶（MMP）与伤口愈合有关。为了分析 MMP-9 和 MMP-13 在伤口愈合中的作用，我们在 MMP-9 敲除 (KO)、MMP-13 KO、MMP-9/13 双 KO 和野生型小鼠中产生全层皮肤伤口。与野生型小鼠相比，所有 KO 小鼠的宏观伤口闭合均延迟。与野生型小鼠相比，MMP-9 KO 和 MMP-13 KO 小鼠的再上皮化速率显着延迟，MMP-9/13 双 KO 小鼠的再上皮化速率显着延迟。野生型小鼠的表皮细胞前缘均表达 MMP-9 和 MMP-13，与对照组相比，用 MMP 抑制剂处理或转染 MMP-9 或 MMP-13 的小干扰 RNA 可抑制角质形成细胞的迁移。 MMP-13 KO 和 MMP-9/13 双 KO 小鼠的伤口肉芽血管密度显着低于野生型小鼠。 MNIP-13 KO 小鼠伤口组织中结缔组织生长因子的降解被暂时阻止。形态测量分析表明，MMP-13 KO 和 MMP-9/13 双 KO 小鼠的伤口收缩和肌成纤维细胞形成均减少。与野生型真皮成纤维细胞相比，MMP-13 KO 小鼠真皮成纤维细胞的增殖和转化生长因子-β1 诱导的肌成纤维细胞分化均减少。这些数据表明，MMP-13 在角质形成细胞迁移、血管生成和伤口愈合收缩中发挥作用，而 MMP-9 在角质形成细胞迁移中发挥作用。 （Am J Pathol 2009,175.-533-546；DOI：10.2353/ajpath.2009.081080）
Matrix metalloproteinases (MMPs) have been implicated in wound healing. To analyze the roles of MMP-9 and MMP-13 in wound healing, we generated full-thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO, and wildtype mice. Macroscopic wound closure was delayed in all of the KO mice, as compared with wild-type mice. The rate of re-epithelialization was significantly delayed in MMP-9 KO and MMP-13 KO mice and remarkably delayed in MMP-9/13 double KO mice, as compared with wild-type mice. Both MMP-9 and MMP-13 were expressed by the leading edges of epidermal cells in wild-type mice, and the migration of keratinocytes was suppressed by treatment with an MMP inhibitor or transfection of small interfering RNAs for MMP-9 or MMP-13, as compared with controls. The vascular density in wound granulation was significantly lower in both MMP-13 KO and MMP-9/13 double KO mice than in wild-type mice. Degradation of connective tissue growth factor in wound tissue was transiently prevented in MNIP-13 KO mice. Morphometric analyses demonstrated a reduction in both wound contraction and inyofibroblast formation in both MMP-13 KO and MMP-9/13 double KO mice. Proliferation and transforming growth factor-beta 1-induced myofibroblast differentiation of dermal fibroblasts from MMP-13 KO mice were decreased, as compared with wild-type dermal fibroblasts. These data suggest that MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in wound healing, while MMP-9 functions in keratinocyte migration. (Am J Pathol 2009,175.-533-546; DOI: 10.2353/ajpath.2009.081080)