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MiR-19a inhibitor improves diabetic retinopathy in rats through PTEN/Akt/P-Akt signaling pathway
1Department of Ophthalmology, First Affilated Hospital of Xi'an Jiaotong University, Xi'an, China.
Abstract:
The aim of this study is to explore the regulatory effect of micro ribonucleic acid (miR)-19a on diabetic retinopathy (DR) through mediating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/protein kinase B (Akt) signaling pathway. Thirty male Sprague-Dawley rats were first divided into Healthy group, DR group and miR-19a inhibitor group. The DR model was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). The retinal tissues were dissected and RGCs were isolated. The expression level of miR-19a therein was determined using quantitative polymerase chain reaction (qPCR). The pathological changes were observed through hematoxylin-eosin staining (HE) staining. The apoptosis was detected by flow cytometry. PTEN was predicted as a target gene of miR-19a through TargetScan biological software. The protein expression of PTEN was detected via immunofluorescence assay. The changes in the phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt pathway-associated proteins were detected using Western blotting. The expression of miR-19a declined substantially in DR rats injected with miR-19a inhibitor (P<0.05). RGCs were arranged regularly, showing apoptosis and milder necrosis in miR-19a inhibitor group. The proportion of apoptotic cells was substantially decreased in miR-19a inhibitor group (P<0.05). It was found that miR-19a inhibitor group exhibited an evidently lower protein expression of PTEN and a higher activation degree of the Akt pathway than DR group (P<0.05). MiR-19a binds to PTEN protein in a targeted manner to mediate the PI3K/Akt pathway, thereby affecting the progression of DR.
Insights
MicroRNA-19a (miR-19a) regulates diabetic retinopathy (DR) by targeting PTEN and modulating the PI3K/Akt pathway. Inhibiting miR-19a reduces retinal cell apoptosis and DR progression.
Area of Science:
- Ophthalmology
- Molecular Biology
- Endocrinology
Background:
- Diabetic retinopathy (DR) is a microvascular complication of diabetes.
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression and are implicated in DR pathogenesis.
- The PTEN/Akt signaling pathway is a key regulator of cell survival and apoptosis, often dysregulated in DR.
Purpose of the Study:
- To investigate the regulatory role of microRNA-19a (miR-19a) in diabetic retinopathy (DR).
- To elucidate the mechanism by which miR-19a mediates the PTEN/Akt signaling pathway in DR.
- To assess the therapeutic potential of modulating miR-19a in a rat model of DR.
Main Methods:
- Establishment of a DR rat model using streptozotocin (STZ) injection.
- Quantification of miR-19a expression using quantitative polymerase chain reaction (qPCR).
- Assessment of retinal pathological changes, RGC apoptosis, PTEN protein expression, and PI3K/Akt pathway activation via HE staining, flow cytometry, immunofluorescence, and Western blotting.
Main Results:
- miR-19a expression was significantly reduced in DR rats, and further decreased with miR-19a inhibitor treatment.
- miR-19a inhibition led to regular arrangement of RGCs, reduced apoptosis and necrosis, and decreased apoptotic cell proportion.
- Inhibition of miR-19a resulted in lower PTEN protein expression and enhanced Akt pathway activation compared to the DR group.
Conclusions:
- miR-19a directly targets PTEN protein, thereby modulating the PI3K/Akt signaling pathway.
- This miR-19a-PTEN-Akt axis plays a critical role in the progression of diabetic retinopathy.
- Targeting miR-19a may represent a novel therapeutic strategy for managing DR.
