Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8)
Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8)
复制标题
DOI：
10.1096/fj.06-7860com
复制
发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
Puente, Xose S.
中科院分区：
文献类型：
--
作者：
Gutierrez-Fernandez, Ana;Inada, Masaki;Puente, Xose S.
基质金属蛋白酶（MMPs）参与了许多组织重塑过程。胶原酶-2（MMP-8）缺陷的小鼠更容易患皮肤癌，这一发现促使我们研究这种蛋白酶在皮肤伤口愈合中的作用。我们已经观察到MMP 8（-/-）小鼠的伤口闭合显著延迟，其伤口中的炎症反应改变，在最初几天中性粒细胞浸润延迟，在随后的时间点持续炎症。这些变化伴随着TGF-β 1信号通路的改变和MMP 8（-/-）小鼠的凋亡缺陷。在MMP 8（-/-）小鼠中观察到的伤口愈合延迟通过来自野生型小鼠的骨髓移植来挽救。对其他MMPs的分析表明，MMP 8（-/-）小鼠的MMP-9表达显著增加，这表明这两种蛋白酶可能在此过程中协同作用。MMP-8和MMP-9在体内形成特异性复合物的新发现进一步支持了这种可能性。总之，这些数据表明MMP-8通过促进炎症的消退而参与伤口修复，并开辟了开发治疗伤口愈合缺陷的新策略的可能性。
Matrix metalloproteinases (MMPs) have been implicated in numerous tissue-remodeling processes. The finding that mice deficient in collagenase-2 (MMP-8) are more susceptible to develop skin cancer, prompted us to investigate the role of this protease in cutaneous wound healing. We have observed a significant delay in wound closure in MMP8(-/-) mice and an altered inflammatory response in their wounds, with a delay of neutrophil infiltration during the first days and a persistent inflammation at later time points. These changes were accompanied by alterations in the TGF-beta 1 signaling pathway and by an apoptosis defect in MMP8(-/-) mice. The delay in wound healing observed in MMP8(-/-) mice was rescued by bone marrow transplantation from wildtype mice. Analysis of other MMPs showed that MMP8(-/-) mice had a significant increase in the expression of MMP-9, suggesting that both proteases might act coordinately in this process. This possibility was further supported by the novel finding that MMP-8 and MMP-9 form specific complexes in vivo. Taken together, these data indicate that MMP-8 participates in wound repair by contributing to the resolution of inflammation and open the possibility to develop new strategies for treating wound healing defects.