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MicroRNA-193-5p modulates angiogenesis through IGF2 in type 2 diabetic cardiomyopathy.

Biochem. Biophys. Res. Commun.2017 Sep 30;491(4):876-882. Epub 2017 Jul 20
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摘要


BACKGROUND: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). METHODS: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. RESULTS: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. CONCLUSION:MiR-193-5p is an active angiogenic factor in diabetic cardiomyopathy, possibly through inverse regulation on its downstream IGF2 gene.

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