Matrix metalloproteinase-9 delays wound healing in a murine wound model.
Matrix metalloproteinase-9 delays wound healing in a murine wound model.
复制标题
DOI：
10.1016/j.surg.2009.10.016
复制
发表时间：
2010-02
期刊：
影响因子：
3.8
通讯作者：
Garner, Warren L.
中科院分区：
文献类型：
--
作者：
Reiss, Matthew J.;Han, Yan-Ping;Garcia, Edwin;Goldberg, Mytien;Yu, Hong;Garner, Warren L.
金属蛋白酶-9（MMP-9）是在慢性伤口中以升高的水平发现的IV型胶原酶。随着伤口愈合，MMP-9减少。在这项研究中，我们调查了MMP-9是否直接有助于慢性伤口的发病机制。使用慢病毒转导的永生化角质形成细胞制备重组proMMP-9。从细胞培养基中纯化ProMMP-9并使用4-氨基苯汞乙酸活化。然后将活性MMP-9悬浮在黄原胶中，使其浓度与在人类慢性伤口中发现的浓度平行。在C57 BL小鼠的背部进行两个平行的6 mm穿孔活组织检查。每天用MMP-9或媒介物处理伤口。在第7、10和12天测量伤口面积，并通过光密度测定、实时RT-PCR、组织学和免疫组织化学检查组织。外源性MMP-9，在慢性伤口内发现的水平，在这个动物模型中延迟伤口愈合。到第7天，MMP-9注射组的伤口比对照伤口大12%（p=0.008）。到第12天，MMP-9注射组的伤口比对照组的伤口大25%（p=0.03）。组织学检查显示，高水平的活性MMP-9损害上皮迁移舌（p=0.0008）。此外，与MMP-9升高一致，舌上皮前缘的IV型胶原减少。MMP-9似乎直接延迟伤口愈合。我们的数据表明，这可能是通过干扰上皮再形成而发生的。我们认为MMP-9干扰基底膜蛋白结构，进而阻碍角质形成细胞迁移、附着和表皮重建。
Metalloproteinase-9 (MMP-9) is a type IV Collagenase found at elevated levels in chronic wounds. As wounds heal, MMP-9 diminishes. In this study, we investigated whether MMP-9 directly contributes to chronic wound pathogenesis. Recombinant proMMP-9 was prepared using immortalized keratinocytes transduced by a lentivirus. ProMMP-9 was purified from cell culture media and activated using 4-aminophenylmercuric acetate. Active MMP-9 was then suspended in Xanthan Gum to a concentration paralleling that found in human chronic wounds. Two parallel 6mm punch biopsies were made on the backs of C57BL mice. Wounds were treated daily with MMP-9 or vehicle. Wound areas were measured and tissues examined by densitometry, real-time RT-PCR, histology, and immunohistochemistry at days 7, 10 and 12. Exogenous MMP-9, at the level found within chronic wounds, delayed wound healing in this animal model. By 7 days, wounds in the MMP-9-injected group were 12% larger than control wounds (p=0.008). By day 12, wounds in the MMP-9-injected group were 25% larger than those of the control group (p=0.03). Histologic examination shows that high levels of active MMP-9 impaired epithelial migrating tongues (p=0.0008). Moreover, consistent with elevated MMP-9, the collagen IV in the leading edge of the epithelial tongue was diminished. MMP-9 appears to directly delay wound healing. Our data suggests that this may occur through interference with re-epithelialization. We propose that MMP-9 interferes with the basement membrane protein structure, which in turn impedes keratinocyte migration, attachment, and the reestablishment of the epidermis.
登录
查看更多内容
影响因子：
3.4
作者：
Daniels, JT;Geerling, G;Saarialho-Kere, U
通讯作者：
Saarialho-Kere, U
影响因子：
4.8
作者：
Han, YP;Tuan, TL;Garner, WL
通讯作者：
Garner, WL
影响因子：
3.6
作者：
Ulrich, D;Lichtenegger, F;Pallua, N
通讯作者：
Pallua, N
影响因子：
6.5
作者：
WYSOCKI, AB;STAIANOCOICO, L;GRINNELL, F
通讯作者：
GRINNELL, F
影响因子：
2.9
作者：
Trengove, Naomi J.;Langton, Simon R.;Stacey, Michael C.
通讯作者：
Stacey, Michael C.