miR‑199a‑3p is involved in the pathogenesis and progression of diabetic neuropathy through downregulation of SerpinE2.
miR‑199a‑3p is involved in the pathogenesis and progression of diabetic neuropathy through downregulation of SerpinE2.
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DOI：
10.3892/mmr.2017.6874
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发表时间：
2017-09
影响因子：
3.4
通讯作者：
Cai Y
中科院分区：
文献类型：
--
作者：
Li YB;Wu Q;Liu J;Fan YZ;Yu KF;Cai Y
本研究旨在探讨miRNA-199 a-3 p在糖尿病神经病变（DN）患者中的表达状况及其参与DN发生的机制。采用逆转录-定量聚合酶链反应（RT-qPCR）方法比较有糖尿病家族史的糖尿病患者和对照志愿者外周血血浆中miRNA-199 a-3 p的表达;在60例糖尿病患者中，45例（75%）的miR-199 a-3 p表达较对照志愿者血浆中上调。采用RT-qPCR方法检测30例DN患者和20例对照组的配对下肢皮肤组织中miR-199 a-3 p的表达，DN患者组miR-199 a-3 p的表达明显高于对照组。接下来，根据糖尿病的临床病理参数评估miR-199 a-3 p表达水平; miR-199 a-3 p表达增加与疾病持续时间（P=0.041）、糖化血红蛋白（HbA 1C）水平（P=0.033）和纤维蛋白原水平（P=0.003）增加显著相关。最后，作为操纵miR-199 a-3 p水平的结果，研究了对下游mRNA表达水平的影响。miR-199 a-3 p过表达抑制细胞外丝氨酸蛋白酶抑制剂E2（SerpinE 2）的表达。因此，可以假设miR-199 a-3 p可以通过下调SerpinE 2促进皮肤外周循环中的凝血而诱导DN。目前的研究结果表明，miR-199 a-3 p可能有潜力作为一个新的治疗靶点，用于治疗糖尿病肾病患者。
The present study aimed to investigate the expression status of miRNA-199a-3p in patients with diabetic neuropathy (DN) and the mechanism by which this miRNA is involved in the genesis of DN. The expression of miRNA-199a-3p in plasma of peripheral blood was compared between patients with diabetes and a family history of diabetes and control volunteers by reverse transcription-quantitative polymerase chain reaction (RT-qPCR); in 60 diabetes patients, 45 (75%) demosntrated upregulated miR-199a-3p expression compared with control volunteer plasma. RT-qPCR was also used to detect miRNA-199a-3p expression in paired lower limb skin tissues from 30 patients with DN and 20 control volunteers; miR-199a-3p expression in patients with DN was significantly higher than in the control group. Next miR-199a-3p expression levels were evaluated with respect to the clinic-pathological parameters of diabetes; increased expression of miR-199a-3p was significantly associated with increased disease duration (P=0.041), glycated hemoglobin (HbA1C) levels (P=0.033), and fibrinogen levels (P=0.003). Finally, the effects on downstream mRNA expression levels were investigated as a result of manipulating miR-199a-3p levels. miR-199a-3p overexpression inhibited the expression of the extracellular serine protease inhibitor E2 (SerpinE2). Therefore, it may be hypothesized that miR-199a-3p can induce DN via promoting coagulation in skin peripheral circulation, through the downregulation of SerpinE2. The present findings suggested that miR-199a-3p may have potential as a novel therapeutic target for the treatment of patients with DN.
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