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Downregulation of miR-130b-3p is associated with the progression of type 2 diabetic nephropathy
Xukai Hua1,2, Xiaoyan Zhu2, Jianzhuo Wu3
1The First School of Clinical Medicine, Southern Medical University Guangzhou, Guangdong, China.
Objective:
To investigate the association between miR-130b-3p and the progression of type 2 diabetic nephropathy (T2DN) and the underlying mechanisms.
Methods:
A total of 279 patients with T2DN were enrolled and divided into the normal albuminuria (NAU) group (n=117), microalbuminuria (MIAU) group (n=98), and the macroalbuminuria (MAAU) group (n=64). Additionally, 80 healthy subjects were selected as the control group. The expression of miR-130b-3p was measured in each group, and the clinical biochemical parameters were recorded. A diabetic nephropathy (DN) rat model was established to further analyze the relationship between miR-130b-3p expression and the Bcl-2/Bax pathway.
Results:
The relative expression level of miR-130b-3p was significantly decreased in patients with type 2 diabetic nephropathy (T2DN). Moreover, its expression in patients of the MAAU group was notably lower than that in patients of the MIAU group. miR-130b-3p in T2DN patients was substantially negatively correlated with the course of disease, HbA1c, HOMA-IR, triglycerides, eGFR, TGF-β1 and TNF-α. Receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic value of miR-130-3p for DN, with an area under the curve (AUC) of 0.854. Compared with the control group, the expression of miR-130b-3p and Bcl-2 in renal tissues of rats in the DN model group was significantly decreased, while the expression of Bax and caspase-3 was significantly increased. Additionally, the number of apoptotic cells in the renal cortex of rats in the DN model group was significantly higher than that in the control group.
Conclusion:
Downregulation of miR-130b-3p in T2DN patients may reflect early renal injury in DN. Its underlying mechanism may involve the induction of apoptosis through the mitochondrial pathway activation, mediated by Bcl-2/Bax imbalance.
Insights
MicroRNA-130b-3p is downregulated in type 2 diabetic nephropathy (T2DN), indicating early kidney injury. Its decrease may promote apoptosis via the Bcl-2/Bax pathway, suggesting a potential biomarker for T2DN progression.
Area of Science:
- Biochemistry
- Molecular Biology
- Nephrology
Background:
- Type 2 diabetic nephropathy (T2DN) is a major complication of diabetes.
- Early detection and understanding of T2DN mechanisms are crucial for effective management.
- MicroRNAs (miRNAs) play significant roles in the pathogenesis of diabetic kidney disease.
Purpose of the Study:
- To investigate the association between miR-130b-3p expression and T2DN progression.
- To explore the underlying molecular mechanisms of miR-130b-3p in T2DN.
- To evaluate the diagnostic potential of miR-130b-3p for DN.
Main Methods:
- Cross-sectional study involving 279 T2DN patients and 80 healthy controls.
- Measurement of miR-130b-3p expression in different T2DN stages (normal albuminuria, microalbuminuria, macroalbuminuria).
- Establishment of a DN rat model to analyze miR-130b-3p expression and its relation to the Bcl-2/Bax pathway and apoptosis.
Main Results:
- miR-130b-3p expression was significantly decreased in T2DN patients, with lower levels in advanced stages.
- Downregulation of miR-130b-3p correlated negatively with disease duration, HbA1c, HOMA-IR, triglycerides, eGFR, TGF-β1, and TNF-α.
- ROC curve analysis showed miR-130b-3p has a diagnostic value for DN (AUC=0.854).
- In DN rats, decreased miR-130b-3p and Bcl-2, increased Bax and caspase-3, and elevated renal cortex apoptosis were observed.
Conclusions:
- Downregulation of miR-130b-3p may serve as an early indicator of renal injury in T2DN.
- The mechanism involves miR-130b-3p influencing apoptosis via the mitochondrial pathway through Bcl-2/Bax imbalance.
- miR-130b-3p holds potential as a biomarker for T2DN progression and severity.
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