Persistent inflammation and angiogenesis during wound healing in K14-directed Hoxb13 transgenic mice.
Persistent inflammation and angiogenesis during wound healing in K14-directed Hoxb13 transgenic mice.
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DOI：
10.1038/jid.2009.305
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发表时间：
2010-03
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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以过度纤维化为特征的慢性、不愈合的伤口和组织修复不足继续对健康和生活质量产生重大负面影响。了解充分愈合所需的分子事件，包括伤口修复的转录控制，对于未来疗法的开发非常重要。我们之前表明，小鼠皮肤中 Hoxb13 的缺失会导致皮肤伤口愈合增强，这表明 Hoxb13 对伤口修复有负面影响。为了测试这一点，我们培育了皮肤特异性 Hoxb13 转基因小鼠，它们通过人角蛋白 14 启动子在表皮基底层过度表达 Hoxb13。使用这些小鼠，我们评估了 Hoxb13 过度表达对皮肤伤口愈合的影响。转基因伤口的特点是纤维蛋白凝块持续存在和长期炎症。值得注意的是，从野生型伤口中清除的中性粒细胞在转基因伤口中仍然很明显。与野生型相比，在转基因伤口边缘观察到明显的表皮增生，并且真皮血管明显异常。 Hoxb13 转基因皮肤中 VEGF 和 TNF-α 均上调。总之，我们的结果确定 Hoxb13 是伤口愈合和其他以异常或过度炎症、血管生成或表皮增殖为特征的病理学的潜在重要临床靶标。
Chronic, non-healing wounds and inadequate tissue repair characterized by excessive fibrosis continue to have a major negative impact on health and quality of life. Understanding the molecular events required for adequate healing, including the transcriptional control of wound repair, will be important for the development of future therapies. We previously showed that loss of Hoxb13 from murine skin results in enhanced cutaneous wound healing, suggesting that Hoxb13 has a negative effect on wound repair. To test this, we generated skin-specific Hoxb13 transgenic mice that overexpress Hoxb13 in the basal layer of the epidermis via the human keratin 14 promoter. Using these mice, we evaluated the effects of Hoxb13 overexpression on cutaneous wound healing. Transgenic wounds were characterized by persistence of the fibrin clot and prolonged inflammation. Notably neutrophils, which had cleared from wild-type wounds, were still pronounced in transgenic wounds. Marked epidermal hyperplasia was observed at transgenic wound edges and dermal vessels were grossly abnormal compared to wild-type. Both VEGF and TNF-α were upregulated in Hoxb13 transgenic skin. Together, our results identify Hoxb13 as a potential important clinical target in wound healing and other pathologies characterized by abnormal or excessive inflammation, angiogenesis, or epidermal proliferation.
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影响因子：
64.8
作者：
GORDON, JR;GALLI, SJ
通讯作者：
GALLI, SJ
影响因子：
4.8
作者：
Hong, YK;Lange-Asschenfeldt, B;Detmar, M
通讯作者：
Detmar, M
影响因子：
7.8
作者：
Banerji, S;Ni, J;Wang, S X;Clasper, S;Su, J;Tammi, R;Jones, M;Jackson, D G
通讯作者：
Jackson, D G
DOI：
10.1084/jem.169.6.1977
发表时间：
1989-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brett J;Gerlach H;Nawroth P;Steinberg S;Godman G;Stern D
通讯作者：
Stern D
影响因子：
6
作者：
Hansen, SL;Myers, CA;Boudreau, N
通讯作者：
Boudreau, N