Li Ying-Bo, Wu Qun, Liu Jie, Fan Yong-Zhi, Yu Kai-Feng, Cai Yi
Department of Pain Management, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.
Mol Med Rep. 2017 Sep;16(3):2417-2424. doi: 10.3892/mmr.2017.6874. Epub 2017 Jun 28.
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.
本研究旨在调查miRNA-199a-3p在糖尿病性神经病变（DN）患者中的表达状况，以及该miRNA参与DN发生的机制。通过逆转录-定量聚合酶链反应（RT-qPCR）比较糖尿病患者及其有糖尿病家族史者与对照志愿者外周血血浆中miRNA-199a-3p的表达；在60例糖尿病患者中，45例（75%）与对照志愿者血浆相比，miR-199a-3p表达上调。RT-qPCR还用于检测30例DN患者和20例对照志愿者配对的下肢皮肤组织中miRNA-199a-3p的表达；DN患者中miR-199a-3p的表达显著高于对照组。接下来，根据糖尿病的临床病理参数评估miR-199a-3p的表达水平；miR-199a-3p表达增加与病程延长（P=0.041）、糖化血红蛋白（HbA1C）水平升高（P=0.033）和纤维蛋白原水平升高（P=0.003）显著相关。最后，研究了通过操纵miR-199a-3p水平对下游mRNA表达水平的影响。miR-199a-3p过表达抑制细胞外丝氨酸蛋白酶抑制剂E2（SerpinE2）的表达。因此，可以推测miR-199a-3p可通过下调SerpinE2，促进皮肤外周循环中的凝血，从而诱导DN。本研究结果表明，miR-199a-3p可能作为治疗DN患者的新型治疗靶点具有潜力。
