Apigenin inhibits angiogenesis of retinal microvascular endothelial cells by regulating miR-140-5p/HDAC3- mediated PTEN/PI3K/AKT pathway

Abstract Background Diabetic retinopathy (DR) is the main reason of visual impairment. Apigenin has anti-angiogenic effects in a variety of diseases. Our aim was to explore the role of apigenin in DR and the mechanism involved. Methods High glucose (HG) induced HRMEC to establish DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. miR-140-5p, HDAC3 and PTEN were detected by qRT-PCR. Western blot measured HDAC3, PTEN and PI3K/AKT pathway related proteins expressions. Cell proliferation and migration were monitored by MTT, wound-healing assay and Transwell assay. Angiogenesis was detected by Tube formation assay. Results After HG treatment, miR-140-5p expression was repressed and miR-140-5p overexpression suppressed HG-induced HRMECs proliferation, migration and angiogenesis. Apigenin treatment significantly reversed the reduction in miR-140-5p level caused by HG treatment and repressed HG-induced HRMECs proliferation, migration and angiogenesis by elevating miR-140-5p. miR-140-5p targeted HDAC3, and overexpression of miR-140-5p could reverse the up-regulation of HDAC3 expression induced by HG treatment. HDAC3 could bind to the promoter region of PTEN and inhibit its expression, and then knocking down HDAC3 suppressed PI3K/AKT pathway via elevating PTEN level. In addition, apigenin inhibited angiogenesis in DR cell models by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Conclusions Apigenin inhibited angiogenesis of HG induced HRMECs by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study might provide new drugs and new targets for treating DR.