Fig. 7
From: MiR-423-5p activated by E2F1 promotes neovascularization in diabetic retinopathy by targeting HIPK2
Knockdown of E2F1 suppressed angiogenesis during DRin vivo. A DR group indicated the unclear retinal structure and the cells were arranged disorderly compared to sham group. Knockdown of E2F1 through sh-E2F1 reversed above pathological changes of retina. B DR group showed the increased VEGF signal in retina while sh-E2F1 suppressed DR-induced increase of VEGF level in retina compared with sh-NC. C DR group displayed the increased levels of E2F1 mRNA, miR-423-5p, and HIF1α mRNA but decreased HIPK2 mRNA level while sh-E2F1 reversed those changes. D Hyperglycemia leads to elevated E2F1, which binds to miR-423-5p promoter and activates its transcription. miR-423-5p directly targets HIPK2 and suppresses HIPK2 expression, leading to disinhibition of HIF1α/VEGF signaling, which promotes neovascularization in DR. All results were presented as the mean ± SD (n = 3). *P < 0.05, **P < 0.01, and ***P < 0.001. DR, diabetic retinopathy; E2F1, E2F transcription factor 1; HIPK2, homeodomain-interacting protein kinase 2; HIF1α, hypoxia inducible factor 1α; VEGF, vascular endothelial growth factor; NC, negative control