Dysregulation of collagen production in diabetes following recurrent skin injury: Contribution to the development of a chronic wound
Dysregulation of collagen production in diabetes following recurrent skin injury: Contribution to the development of a chronic wound
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DOI：
10.1111/wrr.12199
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发表时间：
2014-07-01
影响因子：
2.9
通讯作者：
Liechty, Kenneth W.
中科院分区：
文献类型：
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作者：
Caskey, Robert C.;Zgheib, Carlos;Liechty, Kenneth W.
复发性损伤与慢性糖尿病伤口的发展有关。我们已经开发了一个慢性糖尿病伤口模型的基础上复发性损伤糖尿病小鼠。我们假设mRNA和microRNA水平的胶原蛋白产生失调有助于慢性糖尿病伤口的发展。为了测试这一点，糖尿病和非糖尿病小鼠都经历了复发性损伤。在每次损伤后7天进行TGF-β 1、SMAD-3、Col 1 α 1、Col 3 α 1、microRNA-25和microRNA-29 α的实时PCR以及胶原I和III的蛋白质印迹。糖尿病伤口在所有时间点均显示胶原蛋白减少。这与所有时间点基因和microRNA水平的胶原蛋白产生失调有关。然而，在最终损伤后，糖尿病胶原蛋白的产生显著改善。这似乎是由于两种microRNA的大量减少以及胶原蛋白途径基因表达的增加。在整个创伤过程中，胶原蛋白的产生失调，这表明这是导致慢性糖尿病伤口发展的一个因素。使用该模型的未来研究将允许确定也可能导致慢性糖尿病伤口发展和/或持续的其他因素。
Recurrent injury has been implicated in the development of chronic diabetic wounds. We have developed a chronic diabetic wound model based upon recurrent injury in diabetic mice. We hypothesized that dysregulation of collagen production at both the mRNA and microRNA levels contributes to the development of chronic diabetic wounds. To test this, both diabetic and nondiabetic mice were made to undergo recurrent injury. Real-time PCR for TGF-beta 1, SMAD-3, Col1 alpha 1, Col3 alpha 1, microRNA-25, and microRNA-29a and Western blot for collagen I and III were performed 7 days following each injury. Diabetic wounds displayed decreased collagen at all time points. This was associated with dysregulated collagen production at both the gene and microRNA levels at all time points. Following the final injury, however, diabetic collagen production significantly improved. This appeared to be due to a substantial decrease in both microRNAs as well as an increase in the expression of collagen pathway genes. That dysregulated collagen production progressed throughout the course of wounding suggests that this is one factor contributing to the development of chronic diabetic wounds. Future studies using this model will allow for the determination of other factors that may also contribute to the development and/or persistence of chronic diabetic wounds.