Abstract
ObjectiveDiabetic retinopathy, a common complication of diabetes mellitus and a major cause of blindness. circRNAs spongs target miRNA and thus influencing mRNA expression in DR. We investigated the mechanism of circ_001209 in regulating diabetic retinal vascular dysfunction.MethodsQRT-PCR analysis was performed to detect the expression of miR-15b-5p, COL12A1 and circ_001209 in human retinal vascular endothelial cells (HRVECs) under high glucose conditions. Western blot assay, wound healing assay, transwell assay and tube formation were used to explore the roles of circ_001209/miR-15b-5p/COL12A1 in retinal vascular dysfunction. Bioinformatics analysis and luciferase reporter, RNA-FISH, and overexpression assays were performed to reveal the mechanisms of the circ_001209/miR-15b-5p/COL12A1 interaction. TUNEL staining and H&E staining were used to evaluate the pathological changes in streptozotocin (STZ)-induced DR in rats.ResultsDownregulation of miR-15b-5p under HG conditions promoted proliferation, migration, and tube formation of HRVECs. QRT-PCR and western blot results revealed that miR-15b-5p affected the HRVECs function through targeting COL12A1. Under HG conditions, circ_001209, which acts as a sponge of miR-15b-5p, is upregulated. Besides, overexpression of circ_001209 can affect HRVEC function and aggravate retinal injury in diabetic rats.ConclusionUpregulation of circ_001209 contributes to vascular dysfunction in diabetic retinas through regulating miR-15b-5p and COL12A1, providing a potential treatment strategy for diabetic retinopathy.
Highlights
Diabetic retinopathy (DR), as one of the most common complications of diabetes mellitus (DM), which is the leading cause of vision impairment and even blindness worldwide [1]
MiR‐15b‐5p is low expressed in STZ‐induced diabetic retinopathy tissues and affects function of human retinal vascular endothelial cells (HRVECs) under high‐glucose (HG) conditions
We detected the expression levels of miR-15b-5p in STZ-induced diabetic retinopathy tissues and HRVECs induced by HG
Summary
Diabetic retinopathy (DR), as one of the most common complications of diabetes mellitus (DM), which is the leading cause of vision impairment and even blindness worldwide [1]. It has been reported that miRNAs have a wide range of regulatory functions, including cell proliferation, differentiation, apoptosis, autophagy and other physiological and pathological processes, which may indirectly affect physiological functions and pathological processes of the body [8]. Xue et al [10] found that miR-200-3p plays a protective role in inhibiting the proliferation of diabetic retinopathy cells by blocking the TGF-2/Smad pathway. Ji et al [11] suggested that miR-34a promotes apoptosis of RVECs by targeting SIRT1 in DR rats, which provide a valuable target for DR treatment. In Ye et al [12] reported, miR-15b plays a protective role by regulating the TNF-α/SOCS3 signaling pathway against hyperglycemia-induced retinal endothelial cell apoptosis
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