miR-139-5p promotes neovascularization in diabetic retinopathy by regulating the phosphatase and tensin homolog

다국어 초록 (Multilingual Abstract)

Pathological retinal neovascularization is adriver of the progression of diabetic retinopathy (DR). Thepresent study sought to identify the microRNAs (miRNAs)that are diff erentially expressed during the progression ofDR as well as to explore the specifi c regulatory mechanismof those miRNAs in retinal neovascularization. Using amicroarray data set and a diabetic mouse model, it was determinedthat miR-139-5p was signifi cantly upregulated duringthe progression of DR. The in vitro investigation revealedan elevation in the miR-139-5p level in both the high glucose(HG)-treated mouse retinal microvascular endothelialcells (mRMECs) and the HG-treated human RMECs(hRMECs). The miR-139-5p overexpression elevated cellmigration, facilitated tube formation, and increased vascularendothelial growth factor (VEGF) protein level in thehRMECs. While the angiogenic eff ect of miR-139-5p overexpressionwas halted by an anti-VEGF antibody. Meanwhile,the miR-139-5p knockdown eliminated the VEGFinducedcell migration and tube formation in the hRMECs.
The phosphatase and tensin homolog (PTEN) was the targetgene of the miR-139-5p. PTEN overexpression removed theangiogenic eff ect of miR-139-5p overexpression, which ledto reduced cell migration and tube formation. In the diabeticmice, the miR-139-5p antagomir eff ectively decreased theacellular capillaries and suppressed the formation of aberrantblood vessels in the retinal tissues. Taken together, miR-139-5p promotes retinal neovascularization by repressingPTEN expression.

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