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Limitations of Knockout Mice and Other Tools in Assessment of the Involvement of Matrix Metalloproteinases in Wound Healing and the Means to Overcome Them.
ACS Pharmacology & Translational Science Pub Date : 2020-02-24 , DOI: 10.1021/acsptsci.9b00109
Trung T Nguyen 1 , William R Wolter 2 , Bowen Anderson 1 , Valerie A Schroeder 2 , Ming Gao 1 , Major Gooyit 1 , Mark A Suckow 2 , Mayland Chang 1
Affiliation  

Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice and zymography often confound analysis, which is complicated further as these enzymes exist in three distinct forms with only one being catalytically competent. With the use of topical exogenously administered recombinant MMP-8 and MMP-13 to diabetic and nondiabetic mouse wounds, we show that these proteinases facilitate wound repair by upregulating IL-6 and increasing neutrophil trafficking with an early onset of inflammation. Furthermore, by spatiotemporal control in the use of a selective MMP-2 inhibitor, along with immunoprecipitation and Western blotting, we provide definitive demonstration that MMP-2 does not affect wound healing, contrary to reports. MMP-2 is found in wounds complexed with TIMPs, which is catalytically incompetent.

中文翻译:

淘汰赛小鼠和其他工具在伤口愈合中参与基质金属蛋白酶的评估及其克服方法的局限性。

基质金属蛋白酶(MMP)在伤口愈合中起着重要作用,但是其在伤口修复中的功能归因于挑战。常用的工具(例如MMP敲除小鼠和酶谱分析)经常使分析混乱,因为这些酶以三种不同的形式存在,而其中只有一种具有催化作用,因此使分析变得更加复杂。通过对糖尿病和非糖尿病小鼠伤口局部外用重组MMP-8和MMP-13,我们发现这些蛋白酶通过上调IL-6和增加中性粒细胞的运输促进炎症的早期发作而促进伤口修复。此外,与报道相反,通过使用选择性MMP-2抑制剂进行时空控制以及免疫沉淀和Western印迹,我们提供了明确的证据表明MMP-2不会影响伤口愈合。
更新日期:2020-02-24
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