RKIP negatively regulates the glucose induced angiogenesis and endothelial-mesenchymal transition in retinal endothelial cells

• Published in: Experimental eye research 2019-12, Vol.189, p.107851-107851, Article 107851
• Main Authors: Feng, Le, Zhang, Conghui, Liu, Guodong, Wang, Fang
• Format: Article
• Language: English
• Subjects: Angiogenesis; Capillaries - drug effects; Capillaries - metabolism; Capillaries - pathology; Cell Movement; Cell Proliferation; Cell Survival; Cell viability; Cells, Cultured; Diabetic retinopathy; Diabetic Retinopathy - genetics; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelial to mesenchymal transition; Gene Expression Regulation; Glucose - pharmacology; Humans; Migration; Nerve Tissue Proteins; Phosphatidylethanolamine Binding Protein - biosynthesis; Phosphatidylethanolamine Binding Protein - genetics; Raf kinase inhibitor protein; Retinal Vessels - drug effects; Retinal Vessels - metabolism; Retinal Vessels - pathology; RNA - genetics
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2019.107851

Diabetic retinopathy (DR), a common microvascular complication of diabetes, is reported to be the leading cause of blindness worldwide. In our previous study, we found that the Raf kinase inhibitor protein (RKIP) is significantly decreased in vitreous humor of proliferative diabetic retinopathy (PDR) patients, which indicated that RKIP might play a role in the development of PDR. To investigate the role of RKIP in PDR, stable overexpression and knockdown of RKIP in Human retinal capillary endothelial cells (HRCECs) were generated by using lentivirus constructs. Then, the glucose-induced cell viability, migration, angiogenesis, and (endothelial to mesenchymal transition) EndMT were determined in the RKIP-wide type (WT), -knocking down (KD) and -overexpression (OE) HRCECs. The results showed that, compared with the RKIP-WT groups, the glucose-induced cell viabilities, migration and angiogenesis were significantly increased in the RKIP-KD groups, while significantly decreased in the RKIP-OE groups. Besides, compared with the control groups, CD31 and vWF were upregulated, while α-SMA was downregulated in the RKIP-KD groups, while CD31 and vWF were downregulated, while α-SMA was upregulated in the RKIP-OE groups induced by glucose. In conclusion, our results showed that RKIP negatively regulates glucose-induced cell viability, migration, angiogenesis, and EndMT in HRCECs, suggesting that the downregulation of RKIP in the vitreous humor of PDR patients might contribute to the development of DR. •RKIP negatively regulates glucose-induced cell viabilities and migration of HRCECs.•RKIP negatively regulates glucose-induced angiogenesis of HRCECs.•RKIP negatively regulates glucose-induced endothelial to mesenchymal transition of HRCECs.