MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes
MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes
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DOI：
10.1016/j.bbrc.2017.03.055
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发表时间：
2017-05-20
影响因子：
3.1
通讯作者：
Peng, Haiying
中科院分区：
文献类型：
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作者：
Li, Zhenjie;Jiang, Runxia;Peng, Haiying
背景：在我们的研究中，我们研究了 2 型糖尿病 Goto-Kakizaki (GK) 大鼠心肌微血管内皮细胞 (MMEVC) 中 microRNA-29 的表达和功能。方法：通过 qRT-PCR 比较糖尿病 GK 大鼠 MMEVC 和非糖尿病 Wistar 大鼠 MMEVC 之间的 MiR-29 基因表达。 MiR-29 在 GK MMEVC 中下调，并检查了其对增殖和迁移的血管生成特性的影响。通过 GK MMEVC 中的双荧光素酶报告基因测定、qRT-PCR 和蛋白质印迹评估 miR-29 的潜在下游靶基因胰岛素生长因子 1 (IGF1)。在 miR-29 下调的 GK MMEVC 中，IGF1 也被 siRNA 下调。进一步研究了其对 miR-29 相关血管生成调节对 MMEVC 增殖和迁移的影响。结果：miR-29 在 GK MMEVC 中的表达显着高于 Wistar MMEVC。转染合成的 miR-29 抑制剂成功下调 GK MMEVC 中的内源性 miR-29，随后通过增加细胞增殖和迁移来促进血管生成。 IGF1被证实是GK MMEVC中miR-29的下游靶基因，其基因和蛋白表达在miR-29下调的GK MMEVC中均上调。相反，siRNA介导的IGF1下调逆转了GK MMEVC中miR-29下调的促血管生成作用，因为它减少了细胞增殖和迁移。结论：我们的研究表明，miR-29下调通过其对IGF1基因下游靶标的反向调节，是2型糖尿病大鼠MMEVC中的促血管生成因子。 (C) 2017 年，爱思唯尔公司出版
Background: In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats.Methods: MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC. IGF1 was also downregulated by siRNA in miR-29-downregulated GK MMEVC. Its effect on miR-29-associated angiogenic regulation on MMEVC proliferation and migration was further investigated.Results: MiR-29 was substantially upregulated in GK MMEVC than in Wistar MMEVC. Transfection of synthetic miR-29 inhibitor successfully downregulate endogenous miR-29 in GK MMEVC, and subsequently promoted angiogenesis by increasing cell proliferation and migration. IGF1 was confirmed to be downstream target gene of miR-29 in GK MMEVC, with its gene and protein expressions both upregulated in miR-29-downregualted GK MMEVC. Conversely, siRNA-mediated IGF1 downregulation reversed the pro-angiogenic effect of miR-29 downregulation in GK MMEVC, as it decreased cell proliferation and migration.Conclusion: Our study suggests that miR-29 downregulation, through its inverse regulation on downstream target of IGF1 gene, is a pro-angiogenic factor in MMEVC in type 2 diabetic rats. (C) 2017 Published by Elsevier Inc.