MicroRNA-135b-5p promotes endothelial cell proliferation and angiogenesis in diabetic retinopathy mice by inhibiting Von Hipp-el-Lindau and elevating hypoxia inducible factor α expression

Abstract

Objective

This study was performed to investigate the effect of microRNA-135b-5p (miR-135b-5p) on endothelial cell proliferation and angiogenesis in diabetic retinopathy (DR) mice with the involvement of Von Hipp-el-Lindau protein (VHL) and hypoxia-inducible factor 1 α (HIF1α).

Methods

A DR mouse model was established. The loss- and gain-of-function approaches were conducted to figure out the roles of miR-135b-5p and VHL in vascular hyperplasia, inflammation and apoptosis in DR mice. Endothelial cells were extracted from DR mice and transfected with miR-135b-5p- and VHL-related oligonucleotides and plasmids to decode their functions in cell viability, migration, and tube formation in DR. miR-135b-5p, VHL and HIF-1α expression in mouse retinal tissues and endothelial cells were detected. The targeting connection between miR-135b-5p and VHL was tested.

Results

Elevated miR-135b-5p and HIF-1α, as well as declined VHL existed in DR. Declined miR-135b-5p or overexpressed VHL impaired vascular hyperplasia, inflammation and apoptosis, and decreased HIF-1α expression in DR mice. Repressed miR-135b-5p or up-regulated VHL inhibited viability, migration and tube formation of endothelial cells in DR. miR-135b-5p targeted VHL.

Conclusion

MiR-135b-5p inhibits VHL and elevates HIF1α expression, thereby promoting endothelial cell proliferation and angiogenesis in DR mice.

Keywords:

• Diabetic retinopathy
• microRNA-135b-5p
• Von Hipp-el-Linda
• hypoxia-inducible factor 1 α
• endothelial cell
• proliferation
• angiogenesis

Acknowledgements

The authors acknowledge the reviewers for their helpful comments on this paper.

Ethics approval and consent to participate

The use of all animals was approved by the Experimental Ethics Committee of School of Pharmaceutical Sciences, Jilin University (ethical number: 201804023). Efforts were made to avoid all unnecessary distress to the animals.

Disclosure statement

The authors declare that they have no conflicts of interest.