长链非编码 RNA IGF2AS 的抑制促进 2 型糖尿病中的血管生成。
Inhibition of long noncoding RNA IGF2AS promotes angiogenesis in type 2 diabetes.
机构信息
Department of Cardiology, Second Hospital of Jilin University, Changchun, Jilin Province, 130041, China.
Department of Cardiology, Second Hospital of Jilin University, Changchun, Jilin Province, 130041, China.
出版信息
Biomed Pharmacother. 2017 Aug;92:445-450. doi: 10.1016/j.biopha.2017.05.039. Epub 2017 May 29.
BACKGROUND
In this study, the angiogenic effect of long noncoding RNA (lncRNA), insulin growth factor 2 antisense (IGF2AS) in type 2 diabetes was evaluated.
METHODS
Between Wistar rat and Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes, mRNA expressions of IGF2AS and IGF2 in myocardial microvascular endothelial (mMVE) cells were compared by qRT-PCR. In GK mMVE cells, IGF2AS was inhibited by siRNA. Its effects on cell proliferation and invasion were evaluated by MTT and wound-healing assays. Also, changes of IGF2, VEGF and IGF1 in siRNA-transfected GK mMVE cells were evaluated by qRT-PCR and western blot. In IGF2AS-inhibited GK mMVE cells, IGF2 was further downregulated to evaluate its role in IGF2AS-associated angiogenic regulation, using MTT, wound-healing qRT-PCR and western blot assays, respectively.
RESULTS
IGF2AS was upregulated, whereas IGF2 was downregulated, in diabetic GK mMVE cells. IGF2AS inhibition augmented proliferation and invasion in GK mMVE cells. It also upregulated IGF2 and VEGF (not IGF1) at both molecular and protein levels. Conversely, IGF2 downregulation upregulated IGF2AS and reversely inhibited angiogenic effect of IGF2AS inhibition in GK mMVE cells. It also downregulated VEGF but had no effect on IGF1.
CONCLUSION
IGF2AS inhibition has angiogenic effect in diabetic GK mMVE cells. The functions of IGF2AS in type 2 diabetes are very likely through the inverse regulation of IGF2, but independent of IGF1.
背景
在这项研究中，评估了长链非编码 RNA（lncRNA）胰岛素生长因子 2 反义（IGF2AS）在 2 型糖尿病中的血管生成作用。
方法
在 Wistar 大鼠和 Goto-Kakizaki（GK）大鼠（2 型糖尿病的遗传模型）之间，通过 qRT-PCR 比较 IGF2AS 和 IGF2 在心肌微血管内皮（mMVE）细胞中的 mRNA 表达。在 GK mMVE 细胞中，用 siRNA 抑制 IGF2AS。通过 MTT 和划痕愈合试验评估其对细胞增殖和侵袭的影响。此外，通过 qRT-PCR 和 Western blot 评估转染 siRNA 的 GK mMVE 细胞中 IGF2、VEGF 和 IGF1 的变化。在 IGF2AS 抑制的 GK mMVE 细胞中，进一步下调 IGF2 以评估其在 IGF2AS 相关血管生成调节中的作用，分别使用 MTT、划痕愈合 qRT-PCR 和 Western blot 试验。
结果
糖尿病 GK mMVE 细胞中 IGF2AS 上调，而 IGF2 下调。IGF2AS 抑制增强了 GK mMVE 细胞的增殖和侵袭。它还在分子和蛋白水平上上调 IGF2 和 VEGF（而非 IGF1）。相反，IGF2 下调上调 IGF2AS 并逆转抑制 IGF2AS 抑制在 GK mMVE 细胞中的血管生成作用。它还下调 VEGF，但对 IGF1 没有影响。
结论
IGF2AS 抑制在糖尿病 GK mMVE 细胞中具有血管生成作用。IGF2AS 在 2 型糖尿病中的功能很可能通过 IGF2 的反向调节，但与 IGF1 无关。
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