Long Noncoding RNA GAS5 Regulates Macrophage Polarization and Diabetic Wound Healing
Long Noncoding RNA GAS5 Regulates Macrophage Polarization and Diabetic Wound Healing
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长链非编码RNA GAS5调节巨噬细胞极化和糖尿病伤口愈合
DOI：
10.1016/j.jid.2019.12.030
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发表时间：
2020-08-01
影响因子：
6.5
通讯作者：
Xu, Junwang
中科院分区：
文献类型：
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作者：
Hu, Junyi;Zhang, Liping;Xu, Junwang
糖尿病（Db）伤口的中心特征是慢性炎症的持续存在，这部分是由于促炎（M1）巨噬细胞的长期存在。使用在体内和体外分析，我们已经测试了长的非编码RNA GAS5的Db伤口失调的假设。我们已经评估了GAS5对M1巨噬细胞表型的贡献，以及敲低其表达的功能后果。我们发现GAS5的表达在Db伤口和从Db伤口分离的细胞中显著增加。高脂血症诱导巨噬细胞GAS 5表达。GAS5在体外过表达通过上调信号转导子和转录激活子1促进巨噬细胞向M1表型极化。在我们的判断中最重要的是，GAS 5功能丧失增强了Db伤口愈合。这些数据表明伤口中长非编码RNA GAS 5的相对水平在伤口愈合反应中起关键作用。伤口中GAS 5水平的降低似乎通过促进M1巨噬细胞向M2巨噬细胞的转变来增强愈合。因此，我们的研究结果表明，靶向长的非编码RNA GAS 5可以提供一种治疗干预，以纠正受损的Db伤口愈合。
A central feature of diabetic (Db) wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of proinflammatory (M1) macrophages. Using in vivo and in vitro analyses, we have tested the hypothesis that long noncoding RNA GAS5 is dysregulated in Db wounds. We have assessed the contribution of GAS5 to the M1 macrophage phenotype, as well as the functional consequences of knocking down its expression. We found that expression of GAS5 is increased significantly in Db wounds and in cells isolated from Db wounds. Hyperglycemia induced GAS5 expression in macrophages in vitro. Overexpression of GAS5 in vitro promoted macrophage polarization toward an M1 phenotype by upregulating signal transducer and activator of transcription 1. Of most significance in our judgment, GAS5 loss-of-function enhanced Db wound healing. These data indicate that the relative level of long noncoding RNA GAS5 in wounds plays a key role in the wound healing response. Reductions in the levels of GAS5 in wounds appeared to enhance healing by promoting transition of M1 macrophages to M2 macrophages. Thus, our results suggest that targeting long noncoding RNA GAS5 may provide a therapeutic intervention for correcting impaired Db wound healing.