Yi Fan, Shang Yuqiang, Li Bing, Dai Shilin, Wu Wei, Cheng Long, Wang Xiancan
Department of Cardiac Surgery, The Central Hospital of Wuhan, Wuhan, 430014, China.
Department of Cardiac Surgery, The Central Hospital of Wuhan, Wuhan, 430014, China.
Biochem Biophys Res Commun. 2017 Sep 30;491(4):876-882. doi: 10.1016/j.bbrc.2017.07.108. Epub 2017 Jul 20.
Patients with diabetic cardiomyopathy are often associated with increasing risk of heart failure. In this work, we used animal model to characterize the angiogenic effect of microRNA-193-5p, miR-193-5p in type 2 diabetic Goto-Kakizaki (GK) rats' myocardial microvascular endothelial cells, MMEC(GK).
MiR-193-5p in MMEC(GK) was compared to its expression in Wistar rat MMEC. In MMEC(GK), miR-193-5p was downregulated through viral infection. Its angiogenic effects on MMEC(GK) migration and proliferation were assessed by transwell and MTT assays, respectively. Downstream target of miR-193-5p, insulin growth factor 2 (IGF2), was assessed by dual-luciferase activity, qRT-PCR and western blot assays, respectively. In miR-193-5p-downregulated MMEC(GK), IGF2 was further de-regulated to assess its mechanism in miR-193-5p-downreuglation induced angiogenic regulation.
MiR-193-5p is overexpressed in MMEC(GK). Its downregulation has significantly angiogenic effect by inducing migration and proliferation in MMEC(GK). IGF2 was demonstrated to be directly regulated by miR-193-5p in MMEC(GK). In addition, IGF2 inhibition in miR-193-5p-downregulated MMEC(GK)'s severely hindered cell migration and proliferation.
MiR-193-5p is an active angiogenic factor in diabetic cardiomyopathy, possibly through inverse regulation on its downstream IGF2 gene.
糖尿病性心肌病患者常伴有心力衰竭风险增加。在本研究中，我们使用动物模型来表征微小RNA-193-5p（miR-193-5p）对2型糖尿病Goto-Kakizaki（GK）大鼠心肌微血管内皮细胞（MMEC(GK)）的血管生成作用。
将MMEC(GK)中的miR-193-5p表达与Wistar大鼠MMEC中的表达进行比较。在MMEC(GK)中，通过病毒感染下调miR-193-5p。分别通过Transwell和MTT试验评估其对MMEC(GK)迁移和增殖的血管生成作用。分别通过双荧光素酶活性、qRT-PCR和蛋白质印迹试验评估miR-193-5p的下游靶点胰岛素生长因子2（IGF2）。在miR-193-5p下调的MMEC(GK)中，进一步调节IGF2以评估其在miR-193-5p下调诱导的血管生成调节中的机制。
miR-193-5p在MMEC(GK)中过表达。其下调通过诱导MMEC(GK)的迁移和增殖具有显著的血管生成作用。在MMEC(GK)中，IGF2被证明受miR-193-5p直接调控。此外，在miR-193-5p下调的MMEC(GK)中抑制IGF2会严重阻碍细胞迁移和增殖。
miR-193-5p是糖尿病性心肌病中一种活跃的血管生成因子，可能是通过对其下游IGF2基因的反向调节发挥作用。
