MicroRNA-148a-3p alleviates high glucose-induced diabetic retinopathy by targeting TGFB2 and FGF2
Jihong Wang1, Yong Yao2, Kelei Wang3
1Department of Ophthalmology, Affiliated Hospital of Jiangnan University, No. 200 Huihe Road, Wuxi, 214000, Jiangsu, China. wjh_731128@163.com.
Aims:
Diabetic retinopathy (DR), a common complication of type 1 or type 2 diabetes mellitus, has become the leading cause of blindness among adults in working age. The dysregulation of microRNA has been reported to be strongly related to the initiation or progression of DR. However, neither the biological role nor the molecular mechanism of miR-148a-3p has been researched in DR. This study is designed to investigate the function and mechanism of miR-148a-3p in DR.
Methods:
The bioinformatics analysis (Targetscan: https://www.targetscan.org/vert_72/ ) and numerous experiments including real-time quantitative polymerase chain reaction, terminal deoxynucleotidyltransferase dUTP nick end labeling, CCK-8, western blot, vasculogenesis and luciferase reporter assays were used to research the function and mechanism of miR-148a-3p in DR.
Results:
We constructed DR cell model by treating human retinal microvascular endothelial cells (HRECs) with different concentration gradients of high glucose (HG). Additionally, HG treatment reduced miR-148a-3p level in HRECs. In function, overexpression of miR-148a-3p caused an increase in cell viability and a decrease in cell apoptosis. Besides, miR-148a-3p overexpression led to a damage on blood-retinal barrier (BRB) and suppressed angiogenesis. In mechanism, miR-148a-3p specifically bound to 3' untranslated region of TGFB2 and FGF2. At least, rescue assays demonstrated that the inhibitive influence of miR-148a-3p mimics on BRB injury was offset by overexpression of TGFB2 and the attenuation of angiogenesis resulting from miR-148a-3p mimics was abrogated by overexpression of FGF2 CONCLUSIONS: In a word, we discovered that miR-148a-3p alleviated HG-induced DR by targeting TGFB2 and FGF2. This novel discovery indicated miR-148a-3p as a potential target for DR diagnosis or treatment.
Insights
MicroRNA-148a-3p alleviates high glucose-induced diabetic retinopathy (DR) by targeting TGFB2 and FGF2. This finding suggests miR-148a-3p as a potential therapeutic target for DR.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults.
- MicroRNA dysregulation is implicated in DR initiation and progression.
- The role of miR-148a-3p in DR remains unexplored.
Purpose of the Study:
- To investigate the function and molecular mechanism of miR-148a-3p in diabetic retinopathy.
- To explore miR-148a-3p's potential as a therapeutic target for DR.
Main Methods:
- Bioinformatics analysis (Targetscan) and experimental validation.
- Real-time quantitative PCR, TUNEL, CCK-8, and Western blot assays.
- Vasculogenesis, luciferase reporter assays, and cell model construction using high glucose-treated human retinal microvascular endothelial cells (HRECs).
Main Results:
- High glucose reduced miR-148a-3p levels in HRECs.
- Overexpression of miR-148a-3p increased cell viability, decreased apoptosis, damaged the blood-retinal barrier (BRB), and suppressed angiogenesis.
- miR-148a-3p targets TGFB2 and FGF2, with rescue assays confirming their roles in mediating miR-148a-3p's effects on BRB and angiogenesis.
Conclusions:
- miR-148a-3p alleviates high glucose-induced DR by targeting TGFB2 and FGF2.
- miR-148a-3p demonstrates potential as a diagnostic or therapeutic target for diabetic retinopathy.
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