The role of microRNA-146a in the pathogenesis of the diabetic wound-healing impairment: correction with mesenchymal stem cell treatment.
The role of microRNA-146a in the pathogenesis of the diabetic wound-healing impairment: correction with mesenchymal stem cell treatment.
复制标题
DOI：
10.2337/db12-0145
复制
发表时间：
2012-11
期刊：
影响因子：
7.7
通讯作者：
Liechty KW
中科院分区：
文献类型：
--
作者：
Xu J;Wu W;Zhang L;Dorset-Martin W;Morris MW;Mitchell ME;Liechty KW
糖尿病伤口愈合的损害代表了一个重要的临床问题。慢性炎症被认为在这种损伤的发病机制中起着核心作用。我们以前已经证明，用间充质干细胞（MSC）治疗糖尿病小鼠伤口可以改善愈合，但其机制尚未完全确定。microRNA-146 a（miR-146 a）参与免疫和炎症反应的调节。我们推测miRNA-146 a的异常表达可能与慢性炎症有关。为了验证这一假设，我们检测了基线和损伤后糖尿病和非糖尿病小鼠中miRNA-146 a及其靶基因的表达。糖尿病小鼠伤口中miR-146 a表达显著下调。miR-146 a水平的降低也与其促炎靶基因的基因表达增加密切相关。此外，MSC治疗对糖尿病伤口愈合障碍的纠正与miR-146 a表达水平的显著增加及其促炎靶基因的基因表达降低相关。这些结果提供了第一个证据，即糖尿病伤口中miR-146 a的表达降低可能部分导致糖尿病伤口中观察到的异常炎症反应，并可能导致伤口愈合障碍。
The impairment in diabetic wound healing represents a significant clinical problem. Chronic inflammation is thought to play a central role in the pathogenesis of this impairment. We have previously shown that treatment of diabetic murine wounds with mesenchymal stem cells (MSCs) can improve healing, but the mechanisms are not completely defined. MicroRNA-146a (miR-146a) has been implicated in regulation of the immune and inflammatory responses. We hypothesized that abnormal miRNA-146a expression may contribute to the chronic inflammation. To test this hypothesis, we examined the expression of miRNA-146a and its target genes in diabetic and nondiabetic mice at baseline and after injury. MiR-146a expression was significantly downregulated in diabetic mouse wounds. Decreased miR-146a levels also closely correlated with increased gene expression of its proinflammatory target genes. Furthermore, the correction of the diabetic wound-healing impairment with MSC treatment was associated with a significant increase in the miR-146a expression level and decreased gene expression of its proinflammatory target genes. These results provide the first evidence that decreased expression of miR-146a in diabetic wounds in response to injury may, in part, be responsible for the abnormal inflammatory response seen in diabetic wounds and may contribute to wound-healing impairment.
登录
查看更多内容
影响因子：
--
作者：
Seitz O;Schürmann C;Hermes N;Müller E;Pfeilschifter J;Frank S;Goren I
通讯作者：
Goren I
DOI：
10.1073/pnas.1004204107
发表时间：
2010-08-17
影响因子：
11.1
作者：
Grice, Elizabeth A.;Snitkin, Evan S.;Segre, Julia A.
通讯作者：
Segre, Julia A.
影响因子：
3.5
作者：
Jude, EB;Blakytny, R;Ferguson, MWJ
通讯作者：
Ferguson, MWJ
影响因子：
2.2
作者：
FAHEY, TJ;SADATY, A;SHIRES, GT
通讯作者：
SHIRES, GT
影响因子：
--
作者：
Falanga, Vincent;Iwamoto, Satori;Carson, Polly
通讯作者：
Carson, Polly