Abstract

BackgroundMicroRNA (miRNA) can be used as a biomarker for the early diagnosis of diabetic nephropathy (DN). The purpose of this study was to evaluate the diagnostic value of miR-638 in DN and to analyse its regulatory effect on inflammation.MethodsThis retrospective study involved 98 subjects, including non-diabetic healthy controls (n = 30), patients with type 2 diabetes (T2DM, n = 36) without complications and patients with DN (n = 32). After the anthropometric and biochemical evaluation, serum miR-638 levels were assessed by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The levels of inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha [TNF-α]) were detected using enzyme-linked immunosorbent assay. The Spearman correlations were used to analyze the correlation between miR-638 and urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and inflammatory factors. Furthermore, the receiver operating characteristic (ROC) curve was used to measure the diagnostic value of miR-638 in DN. Human mesangial cells (HMCs) were treated with normal glucose (NG, 5.5 mM glucose), high glucose (HG, 30 mM glucose), or high osmotic pressure solution (HO, 5.5 mM glucose + 24.5 mM mannitol) in vitro to simulate the hyperglycamic state in vivo. Subsequently, the HMCs were transfected with miR-638 mimics to regulate the level of miR-638 in the cells and detect its regulation on cell inflammation and proliferation.ResultsCompared with healthy controls and patients with T2DM, serum miR-638 in patients with DN was significantly lower. The reduced miR-638 expression has a significant diagnostic value, which can significantly distinguish patients with DN from healthy controls or patients with T2DM. Inflammatory factors were significantly upregulated in patients with DN and negatively correlated with miR-638 levels. In addition, miR-638 was negatively correlated with UAE and positively correlated with eGFR. HG decreased the level of miR-638 and promoted the expression of inflammatory factors and proliferation in HMCs. However, miR-638 mimic significantly decreased the levels of inflammatory factors and inhibited the proliferative ability induced by HG.ConclusionsSerum miR-638 expression was low in DN and can be a potentially valuable biomarker for DN. This miRNA seems to influence inflammatory responses and participate in the progression of DN by regulating proliferation.

Highlights

  • The incidence of type 2 diabetes mellitus (T2DM) is rapidly increasing worldwide and is estimated to increase to 10.4% by 2040 [1]

  • There were no significant differences in age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC levels and triglyceride levels among the three groups (P > 0.05)

  • fasting blood glucose (FBG), IL-1β, IL-6, and tumor necrosis factor α (TNF-α) levels and urinary albumin excretion (UAE) were significantly increased, whereas estimated glomerular filtration rate (eGFR) was significantly decreased compared with patients with T2DM (P < 0.05)

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Summary

Introduction

The incidence of type 2 diabetes mellitus (T2DM) is rapidly increasing worldwide and is estimated to increase to 10.4% by 2040 [1]. (DN) is one of the most important chronic complications of T2DM, and the main cause of end-stage renal disease (ESRD) and death in patients with diabetes [2]. DN is a powerful risk factor for complications such as cardiovascular disease (myocardial infarction, stroke, atherosclerosis, and hypertension), neuropathy, and kidney disease [5]. This disease is believed to be caused by factors such as genetic susceptibility, glucose metabolism disorder, renal hemodynamics changes, oxidative stress, and cytokines [6]. MicroRNA (miRNA) can be used as a biomarker for the early diagnosis of diabetic nephropathy (DN). The purpose of this study was to evaluate the diagnostic value of miR-638 in DN and to analyse its regulatory effect on inflammation

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