The diagnostic value and mechanism of miR-127-3p in type 2 diabetes and complications of diabetic nephropathy.

BACKGROUND

Diabetic kidney disease (DKD) is a serious microvascular complication of type 2 diabetes mellitus (T2DM). miR-127-3p is dysregulated in T2DM, but the specific molecular mechanism remains unclear. We aim to probe the diagnostic value of miR-127-3p and its molecular mechanism in T2DM and DKD.

METHODS

This study comprised 218 individuals, including 78 patients with T2DM, 72 patients with DKD and 68 healthy controls. All participants underwent fasting peripheral blood collection. In vitro, we simulated a hyperglycemic environment by treating human mesangial cells (HMC) with high-concentration glucose (HG). Subsequently, RT-qPCR was used to detect the levels of miR-127-3p in serum and HMC. Cell viability and inflammatory cytokine (TNF-α, IL-1β and IL-6) levels were assessed using the CCK-8 assay and ELISA, respectively. The dual-luciferase reporter assay validated the target relationship between miR-127-3p and ACO2.

RESULTS

By comparing baseline clinical characteristics, we identified significant differences among the three groups in high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR) and albuminuria. Additionally, miR-127-3p was elevated in T2DM and DKD patients. It could distinguish healthy individuals from T2DM or T2DM from DKD. In HG-induced HMC, miR-127-3p inhibitor elevated the cell viability and the levels of SOD while suppressing the levels of MDA. These effects were abolished by ACO2 silencing. Furthermore, downregulated miR-127-3p reduced the levels of TNF-α, IL-1β and IL-6. sh-ACO2 alleviated the inhibitory effects of miR-127-3p.

CONCLUSIONS

Upregulated miR-127-3p was involved in the progression of T2DM and DKD. In HG-induced HMC, down-regulated miR-127-3p improved cell viability and suppressed oxidative stress and inflammatory responses by negatively regulating ACO2.