Conclusion
Collectively, the present study pinpointed the involvement of miR-30b delivered by plasma-EVs in PDR angiogenesis, thus laying the basis for the development of novel therapeutic targets for the treatment of PDR.
Methods
The expression of microRNA-30b (miR-30b) was quantified in a streptozotocin (STZ)-induced mouse model of PDR. The binding affinity between SIRT1 and miR-30b was then identified and validated. After transduction with In-miR-30b or combined with sh-SIRT1, high-glucose (HG)-induced retinal microvascular endothelial cells (RMECs) were co-cultured with extracellular vesicles (EVs) derived from the plasma of PDR mice (plasma-EVs). The proliferation and angiogenesis of RMECs were then detected in vitro.
Purpose
Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication, characterized by pathological angiogenesis. This study sets out to investigate the potential molecular mechanism in the angiogenesis during PDR.
Results
miR-30b expression was upregulated in the retinal tissue of PDR mice. SIRT1 was a target gene of miR-30b and under the negative regulation by miR-30b in RMECs. In contrast, inhibition of miR-30b resulted in elevated SIRT1 expression, thus alleviating the angiogenesis of RMECs. miR-30b was enriched in the plasma-EVs and could be delivered to RMECs, in which miR-30b exerted pro-angiogenic effects. Furthermore, inhibition of miR-30b arrested the progression of PDR in mice by promoting the expression of SIRT1.