miR-372-3p is a potential diagnostic factor for diabetic nephropathy and modulates high glucose-induced glomerular
Zhiyun Meng1, Fangyuan Li1, Bin Wang1
1Department of Nephrology, Weifang City Traditional Chinese Medical Hospital, Weifang, Shandong Province, China.
Introduction:
Previous studies have reported that microRNAs are implicated in the pathogenesis of diabetic nephropathy (DN). In this study, the underlying molecular mechanisms and diagnostic significance of miR-372-3p were investigated in the process of DN.
Material And Methods:
Cell proliferation and apoptosis were measured using MTT and Annexin V-FITC double staining, respectively. RT-qPCR and western blotting were used to measure the expression levels of mRNA and protein. The diagnostic power of miR-372-3p in plasma for DN was evaluated using the receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC).
Results:
miR microarray analysis revealed that 126 miRs were significantly differentially expressed in response to high glucose stimulation. Among these miRs, high glucose stimulated miR-372-3p expression at the highest level. In vitro experimental measurements showed that knockdown of miR-372-3p showed the ability to reverse high glucose-induced glomerular endothelial cell apoptosis and impairment of eNOS/NO bioactivity. Mechanistic analysis revealed that fibroblast growth factor-16 (FGF-16) as a direct of miR-372-3p protected against high glucose-induced glomerular endothelial cell dysfunction. ROC analysis revealed that the diagnostic value of miR-372-3p, miR-15a or miR-372-3p combined with miR-15a in type 2 diabetes mellitus patients (AUC = 0.841, p < 0.001; AUC = 0.822, p < 0.001 or AUC = 0.922, p < 0.001) with DN was better than in type 1 diabetes mellitus patients (AUC = 0.805, p < 0.001; AUC = 0.722, p < 0.001 or AUC = 0.865, p < 0.001) with DN.
Conclusions:
miR-372-3p might be a valuable therapeutic target and diagnostic marker for patients with DN.
Insights
MicroRNA-372-3p plays a key role in diabetic nephropathy (DN) pathogenesis by regulating cell apoptosis and protecting against high glucose-induced damage. This microRNA shows promise as a diagnostic marker for DN in diabetic patients.
Area of Science:
- Molecular Biology
- Genetics
- Nephrology
Background:
- MicroRNAs (miRNAs) are increasingly recognized for their role in the pathogenesis of diabetic nephropathy (DN).
- Understanding the specific mechanisms and diagnostic potential of individual miRNAs is crucial for managing DN.
- miR-372-3p has been identified as a potential player in DN development.
Purpose of the Study:
- To investigate the molecular mechanisms of miR-372-3p in diabetic nephropathy.
- To evaluate the diagnostic significance of miR-372-3p in patients with DN.
- To explore miR-372-3p as a potential therapeutic target for DN.
Main Methods:
- Microarray analysis to identify differentially expressed miRNAs under high glucose conditions.
- In vitro experiments including cell proliferation (MTT) and apoptosis assays (Annexin V-FITC).
- Quantitative real-time PCR (RT-qPCR) and Western blotting to measure gene and protein expression.
- Receiver Operating Characteristic (ROC) curve analysis to assess diagnostic value.
Main Results:
- High glucose stimulation significantly upregulated miR-372-3p expression.
- Knockdown of miR-372-3p reversed high glucose-induced glomerular endothelial cell apoptosis and improved eNOS/NO bioactivity.
- Fibroblast growth factor-16 (FGF-16) was identified as a direct target of miR-372-3p, protecting against cellular dysfunction.
- miR-372-3p demonstrated significant diagnostic value for DN in both type 1 and type 2 diabetes mellitus patients, with combined use with miR-15a showing the highest AUC (0.922).
Conclusions:
- miR-372-3p is implicated in the molecular mechanisms underlying DN.
- miR-372-3p exhibits potential as a diagnostic biomarker for DN.
- miR-372-3p represents a promising therapeutic target for DN treatment.
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