microRNA-216a protects against human retinal microvascular endothelial cell injury in diabetic retinopathy by suppressing the NOS2/JAK/STAT axis.

Objective: Since microRNAs (miRNAs) represent as effective therapeutic targets for diabetic retinopathy (DR), we identified aberrantly expressed miRNAs related to cellular dysfunction in DR and further detected their potential targets. This study aimed to explore the synergistic effect of miR-216a, inducible nitric oxide synthase 2 (NOS2) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway on human retinal microvascular endothelial cell (HRMEC) injury in DR.
Methods: The differentially expressed genes in DR were obtained by GEO database, and the downstream signaling pathways and upstream targeted miRNAs were obtained through bioinformatics analysis. Subsequently, a DR model rat was established, and the target miR-216a was overexpressed to observe the pathological and morphological changes of the rat retina and the levels of inflammatory factors. Then, HRMECs were extracted and added with d-Glucose, and then transfected with miR-216a, NOS2 or adding JAK/STAT signaling pathway specific inhibitor to observe changes in cell activity and inflammatory damage.
Results: NOS2 was significantly upregulated, and the JAK/STAT signaling pathway was significantly activated in DR. miR-216a targeted NOS2, which played a protective role in the retina of DR rats. Moreover, in cell experiments, overexpression of miR-216a promoted the viability of HRMECs under d-glucose treatment, and inhibited NOS2 expression and the JAK/STAT signaling pathway activation.
Conclusion: This study suggests that miR-216a protects against HRMECs injury in DR by suppressing the NOS2/JAK/STAT axis.
Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interests in this study.
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