| Objective:IgA nephropathy(IgAN)is the most common primary glomerulonephritis worldwide.The clinical diagnosis of IgAN requires renal biopsy and there is a certain risk.There is no early and non-invasive diagnosis of IgAN.Our study is to identify plasma microRNAs(miRNAs)differently expressed between IgAN patients and normal controls(NC)and whether it can serve as diagnostic biomarkers.Methods:Quantitative reverse transcription polymerase chain reaction(qRT-PCR)based Exiqon panel(miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M)was used to perform expression profiling of peripheral plasma miRNAs from pooled samples(2 IgAN pools vs.1 NC pool)in the screening phase.The different expression levels were then validated through training(32 IgAN vs.31 NCs)and testing stages(51 IgAN vs.51 NCs)by relative quantification methods using qRT-PCR.The renal pathological lesions of patients with IgAN were evaluated according to Lee's grading system.Finally,the relationship between the obtained miRNAs and renal pathology and clinical parameters was explored.Results:A total of 48 miRNAs were identified through the initial screening phase.These miRNAs were assessed in the training stage followed by validation in the testing stage.We discovered a plasma miRNA signature including four up-regulated miRNAs(miR-148a-3p,miR-150-5p,miR-20a-5p and miR-425-3p)and the areas under the receiver operating characteristic(ROC)curve(AUC)were 0.80 and 0.76 for the training and testing stage,respectively.The expression of the four miRNAs in IgAN grade I-II subgroups(according to Lee's grading system)was obviously higher than that in IgAN grade III-V(P<.05).Plasma levels of miR-148a-3p were positively correlated with eGFR(r = 0.25,P = 0.02).Conclusion:In summary,the plasma expression of miR-148a-3p,miR-150-5p,miR-20a-5p and miR-425-3p were up-regulated in patients with IgAN,especially the early-stage disease.Further studies are needed to explore the roles of the four miRNAs in the pathogenesis and progression of IgAN.Objective:Long-term peritoneal dialysis is accompanied by functional and histopathological alterations in the peritoneal membrane.In the long process of peritoneal dialysis,high-glucose peritoneal dialysis solution(HGPDS)will aggravate the peritoneal fibrosis,leading to decreased effectiveness of peritoneal dialysis and ultrafiltration failure.The purpose of this study was to investigate the role of autophagy in peritoneal injury in patients undergoing long-term peritoneal dialysis,and its relationship with epithelial-mesenchymal transition(EMT),apoptosis,and fibrosis.Materials and Methods:The peritoneal membranes from patients were performed with immunocytochemistry and transmission electron microscopy.Human peritoneal mesothelial cells were treated with 1.5%,2.5%,and 4.25%HGPDS for 24 hours;Human peritoneal mesothelial cells pretreated with TGF-p 1(10 ng/ml)or transfected with siRNA Beclinl were treated with 4.25%HGPDS or vehicle for 24 hours.We further detected the production of TGF-p 1,activation of TGF-?1/Smad2/3 signaling,induction of autophagy,EMT,apoptosis andfibrosis.We also explored whether autophagy inhibition by siRNA targeting Beclin 1 reduces EMT,apoptosis,and fibrosis in human peritoneal mesothelial cells.Results:HGPDS increased TGF-? 1 production,activated TGF-? 1/Smad2/3 signaling and induced autophagy,apoptosis and fibrosis hallmarks in human peritoneal mesothelial cells;HGPDS induced Beclin 1-dependent autophagy in human peritoneal mesothelial cells;Autophagy inhibition by siRNA Beclin 1 reduced EMT,apoptosis and fibrosis in human peritoneal mesothelial cells.Conclusions:Autophagy inhibition by siRNA Beclin 1 reduced HGPDS induced EMT,apoptosis and fibrosis in human peritoneal mesothelial cells.Taken all together,these studies are expected to open a new avenue in the understanding of peritoneal fibrosis,which may guide us to explore the compounds targeting autophagy and achieve the therapeutic improvement of PD. |
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