BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
文摘目的分析血清微小核糖核酸(micro RNA,miR)-139-5p,组蛋白去乙酰化酶4(histone deacetylase 4,HDAC4)和胶质纤维酸性蛋白(glialfibrillary acidic protein,GFAP)与新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)脑损伤严重程度的关系。方法选取2017年1月~2022年3月广元市中心医院分娩的HIE新生儿72例为研究对象(研究组);同期健康的足月新生儿75例为对照组。实时荧光定量PCR检测血清中miR-139-5p,HDAC4表达水平。酶联免疫吸附法(ELISA)检测血清GFAP水平。Logistic回归分析影响HIE患儿重度脑损伤发生的因素。结果与对照组相比,研究组血清GFAP(1.30±0.37ng/L vs 0.50±0.15ng/L),HDAC4相对表达水平(2.05±0.39 vs 1.02±0.21)升高,miR-139-5p相对表达水平(0.63±0.14 vs 1.01±0.22)和NBNA评分(33.20±1.43分vs 39.85±2.23分)降低,差异具有统计学意义(t=17.304,20.046,12.436,21.424,均P<0.05);与轻中度组相比,重度组血清GFAP(1.61±0.47ng/L vs 1.16±0.33ng/L),HDAC4(2.43±0.37 vs 1.87±0.40)相对表达水平升高,miR-139-5p相对表达水平(0.38±0.10 vs 0.74±0.16)和NBNA评分(30.52±1.54分vs 34.46±1.38分)降低,差异具有统计学意义(t=4.690,5.669,9.900,10.884,均P<0.05)。Logistic回归分析显示,miR-139-5p低表达,HDAC4高表达,低NBNA评分,低出生后1 min内Apgar评分是影响HIE患儿重度脑损伤发生的危险因素(Waldχ^(2)=5.772~6.969,OR=1.519~1.709,均P<0.05)。Pearson分析显示,血清miR-139-5p表达水平与GFAP,HDAC4呈负相关(r=-0.416,-0.579,均P<0.05),血清HDAC4表达水平与GFAP呈正相关(r=0.437,P<0.05)。Spearman分析显示,血清mi R-139-5p表达水平与NBNA评分、出生后1 min内Apgar评分、出生后5 min内Apgar评分呈正相关(r=0.398,0.367,0.348,均P<0.05);血清HDAC4表达水平与NBNA评分、出生后1 min内Apgar评分、出生后5 min内Apgar评分呈负相关(r=-0.364,-0.345,-0.332,均P<0.05)。结论HIE患儿血清中miR-139-5p表达降低,HDAC4表达升高,mi R-139-5p,HDAC4与HIE患儿脑损伤严重程度有关。
