Exosomes derived from BMSCs alleviates high glucose-induced diabetic retinopathy via carrying miR-483-5p
Dan Cao1, Liang Zhou1, Rong Hu2
1Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, People's Republic of China.
Abstract:
Diabetic retinopathy (DR) is a progressive disease which can cause health problem. It has been reported that bone marrow mesenchymal stem cells (BMSCs)-secreted exosomes could regulate the progression of DR via carrying microRNAs. Meanwhile, miR-483-5p was downregulated in DR; however, whether BMSCs-secreted exosomes can modulate DR progression via carrying miR-483-5p remains unclear. To mimic DR in vitro, ARPE-19 cells were exposed to 30 mM high glucose (HG). Exosomes were isolated from BMSCs and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Cell counting kit-8 assay was applied for assessing the cell viability. Flow cytometry was applied to test the cell apoptosis. Meanwhile, dual luciferase assay was used to evaluate the association among miR-483-5p and downstream target insulin-like growth factor 1 receptor (IGF-1R). In addition, quantitative reverse-transcription polymerase chain reaction and western blot were used for exploring the level of miR-483-5p and IGF-1R. HG significantly induced apoptosis in ARPE-19 cells, while BMSCs-derived exosomes reversed this phenomenon. In addition, inhibition of miR-483-5p expression of exosomes further aggravated HG-induced ARPE-19 cell apoptosis. Meanwhile, IGF-1R was the downstream messenger RNA of miR-483-5p, and IGF-1R silencing could reverse the effect of exosomes with downregulated miR-483-5p on HG-induced cell injury. Exosomes derived from BMSCs inhibit the progression of DR via carrying miR-483-5p. Thus, our study might provide a theoretical basis for discovering new strategies against DR.
Insights
Bone marrow mesenchymal stem cell exosomes carrying miR-483-5p inhibit diabetic retinopathy (DR) progression. This finding offers a new therapeutic strategy for DR by protecting retinal cells from high glucose-induced damage.
Area of Science:
- Ophthalmology
- Cell Biology
- Biotechnology
Background:
- Diabetic retinopathy (DR) is a progressive complication of diabetes.
- Bone marrow mesenchymal stem cells (BMSCs)-secreted exosomes show potential in regulating DR.
- The role of miR-483-5p within these exosomes in DR remains largely unknown.
Purpose of the Study:
- To investigate whether BMSCs-derived exosomes carrying miR-483-5p can modulate the progression of diabetic retinopathy (DR).
- To explore the underlying mechanism involving insulin-like growth factor 1 receptor (IGF-1R).
Main Methods:
- ARPE-19 cells were treated with high glucose (HG) to mimic DR in vitro.
- Exosomes were isolated from BMSCs and characterized.
- Cell viability, apoptosis, miR-483-5p, and IGF-1R levels were assessed using assays like CCK-8, flow cytometry, qRT-PCR, and Western blot.
- Dual luciferase assay confirmed the interaction between miR-483-5p and IGF-1R.
Main Results:
- HG induced significant apoptosis in ARPE-19 cells.
- BMSCs-derived exosomes protected ARPE-19 cells from HG-induced apoptosis.
- Inhibition of miR-483-5p in exosomes exacerbated cell apoptosis.
- IGF-1R was identified as a direct target of miR-483-5p, and its silencing reversed the protective effects of exosomes with downregulated miR-483-5p.
Conclusions:
- BMSCs-derived exosomes inhibit DR progression by delivering miR-483-5p.
- The miR-483-5p/IGF-1R axis is a key mechanism in the protective effect of these exosomes.
- This study provides a theoretical basis for novel therapeutic strategies against diabetic retinopathy.
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