Differential Expression of HIF-1α in Skin and Mucosal Wounds
Differential Expression of HIF-1α in Skin and Mucosal Wounds
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DOI：
10.1177/0022034512454435
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发表时间：
2012-09-01
影响因子：
7.6
通讯作者：
DiPietro, L. A.
中科院分区：
文献类型：
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作者：
Chen, L.;Gajendrareddy, P. K.;DiPietro, L. A.
尽管上皮加速闭合，口腔粘膜伤口表现出较低水平的VEGF和更精细的血管生成反应比皮肤伤口。血管生成的特殊差异表明，皮肤和口腔粘膜伤口可能经历不同水平的缺氧和HIF-1 α。使用小鼠背部皮肤和舌头的类似伤口模型，我们确定了缺氧和HIF-1 α的水平。皮肤伤口明显比粘膜伤口更缺氧，HIF-1 α水平也更高。此外，在应激条件下，皮肤伤口，而不是粘膜伤口，表现出HIF-1 α比非应激水平进一步升高。为了确定是否操纵氧水平可以平衡每个组织的修复反应，我们在小鼠受伤后将其暴露于高压氧治疗（HBOT）。HBOT没有显著改变皮肤或粘膜伤口中HIF-1 α或VEGF的表达，也没有改变伤口床的血管分布。这些研究表明，皮肤伤口比粘膜伤口具有更高水平的缺氧，并且HIF-1 α的表达存在差异。有趣的是，HBOT对氧的调节并不能改善这种差异。这些结果表明，对缺氧的不同反应可能是皮肤和口腔粘膜中不同的伤口愈合表型的基础。
Despite accelerated epithelial closure, oral mucosal wounds exhibit lower levels of VEGF and a more refined angiogenic response than do skin wounds. The specific differences in angiogenesis suggest that skin and oral mucosal wounds may experience dissimilar levels of hypoxia and HIF-1 alpha. Using a model of comparable wounds on murine dorsal skin and tongue, we determined levels of hypoxia and HIF-1 alpha. Skin wounds were found to be significantly more hypoxic and had higher levels of HIF-1 alpha than mucosal wounds. Furthermore, under stressed conditions, skin wounds, but not mucosal wounds, exhibited a further elevation of HIF-1 alpha beyond that of non-stressed levels. To determine if manipulation of oxygen levels might equalize the repair response of each tissue, we exposed mice to hyperbaric oxygen treatment (HBOT) following wounding. HBOT did not significantly change HIF-1 alpha or VEGF expression in either skin or mucosal wounds, nor did it alter wound bed vascularity. These studies suggest that skin wounds have higher levels of hypoxia than do mucosal wounds, along with a differential expression of HIF-1 alpha. Interestingly, modulation of oxygen by HBOT does not ameliorate this difference. These results suggest that differential responses to hypoxia may underlie the distinctive wound-healing phenotypes seen in skin and oral mucosa.