Deletion of a tumor necrosis superfamily gene in mice leads to impaired healing that mimics chronic wounds in humans.
Deletion of a tumor necrosis superfamily gene in mice leads to impaired healing that mimics chronic wounds in humans.
复制标题
小鼠肿瘤坏死基因的缺失导致愈合受损，该愈合模仿了人类的慢性伤口。
DOI：
10.1111/j.1524-475x.2012.00785.x
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Martins-Green MM
中科院分区：
文献类型：
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作者：
Petreaca ML;Do D;Dhall S;McLelland D;Serafino A;Lyubovitsky J;Schiller N;Martins-Green MM
皮肤伤口的适当愈合要经历一系列重叠的阶段。无法愈合的伤口在这些过程中有一个或多个是有缺陷的，是一个主要的临床问题。开发慢性创面治疗方法的一个关键问题是缺乏动物模型来研究愈合缺陷的潜在机制。在这里，我们发现肿瘤坏死因子超家族成员14(TNFSF14/LIGHT)的缺失会导致小鼠创面受损，具有非慢性和慢性溃疡的特征。这些创面显示：(1)过度产生细胞因子，特别是三种趋化因子(KC/CXCL8、MCP-1/CCL2、IP-10/CXCL10)，这可能是炎症异常启动和消退的关键；(2)基底膜缺陷，解释了血管渗漏和真皮/表皮相互作用的中断；(3)肉芽组织中含有高水平的Coll III，而Coll I几乎不存在，也不形成纤维。我们还看到了非慢性伤口和慢性伤口之间的主要区别，后者由细菌膜填充，并产生嗜酸性粒细胞趋化因子，这是一种趋化因子，吸引白细胞对抗多细胞生物体(生物膜可以被认为是)。这一新的小鼠模型捕获了在受损和慢性人类伤口中观察到的许多缺陷，并提供了一种工具来解决其潜在的细胞和分子机制。
Proper healing of cutaneous wounds progresses through a series of overlapping phases. Non-healing wounds are defective in one or more of these processes and represent a major clinical problem. A critical issue in developing treatments for chronic wounds is the paucity of animal models to study the mechanisms underlying the defects in healing. Here we show that deletion of Tumor Necrosis Factor Superfamily Member 14 (TNFSF14/LIGHT) leads to impaired wounds in mice that have the characteristics of non-chronic and chronic ulcers. These wounds show: (1) Excessive production of cytokines, in particular three chemokines (KC/CXCL8, MCP-1/CCL2, IP-10/CXCL10), that may be key to the abnormal initiation and resolution of inflammation; (2) defective basement membranes, explaining blood vessel leakage and disruption of dermal/epidermal interactions; (3) granulation tissue that contains high levels of Coll III whereas Coll I is virtually absent and does not form fibrils. We also see major differences between non-chronic and chronic wounds, with the latter populated by bacterial films and producing eotaxin, a chemokine that attracts leukocytes that combat multicellular organisms (which biofilms can be considered to be). This new mouse model captures many defects observed in impaired and chronic human wounds, and provides a vehicle to address their underlying cell and molecular mechanisms.