目的:探讨miRNA-21调控JAK2/STAT3信号通路对IgA肾病模型大鼠肾纤维化的影响.方法:建立IgA肾病大鼠模型,清洁级SD雄性大鼠40只分为空白对照组(A组)、IgA肾病模型组(IgAN,B组)、模型组+NC antagomir组(C组)和模型组+miRNA-21 antagomir组(D组),每组10只.检测24 h尿蛋白、血清尿素氮及血肌酐,HE染色观察肾脏组织病理学改变,qRT-PCR法检测血清及肾组织miRNA-21和STAT3的mRNA表达水平,Western blot检测肾脏JAK2、p-JAK2、STAT3和p-STAT3蛋白表达水平,ELISA检测肾组织TGF-β1和MMP-9含量.结果:A组大鼠肾小球基质无明显增生,肾小管及间质未见明显异常;B组和C组大鼠肾小球系膜间质明显增生,间质明显纤维化伴炎性细胞浸润;D组大鼠肾小球系膜间质增生减少,肾间质内纤维化水平及炎性细胞浸润明显减少.与A组相比,B组、C组和D组大鼠24 h尿蛋白及BUM均显著升高,血清及肾组织miRNA-21及STAT3 mRNA表达水平显著升高,肾组织JAK2、p-JAK2、STAT3、p-STAT3蛋白表达水平及TGF-β1、MMP-9含量均显著升高,差异均具有统计学意义(P<0.05);与C组相比,D组大鼠24 h尿蛋白及BUM均显著降低,血清及肾组织miRNA-21及STAT3的mRNA表达水平及肾组织JAK2、p-JAK2、STAT3、p-STAT3的蛋白表达水平、TGF-β1、MMP-9的含量均显著降低(P<0.05).结论:抑制miRNA-21可改善IgA肾病大鼠肾组织损伤,可能与miRNA-21调控JAK2/STAT3信号通路及TGF-β1、MMP-9的蛋白表达有关.

Objective:To investigate the role of miRNA-192 in the regulation of Wilms′ tumor 1 protein (WT1) induced epithelial-mesenchymal transition (EMT) in podocytes.Methods:Human glomerular podocytes were divided into four groups: blank control group, high glucose group, negative control group, miRNA-192 inhibition group. Western blotting was used to detect the expression level of the surface marker proteins nephrin, WT1, transforming growth factor-β1(TGF-β1) and α-smooth muscle actin(α-SMA) in podocytes of each group. The expression of miRNA-192 and WT1 mRNA in each group were detected by qRT-PCR. The targeting relationship between miRNA-192, WT1, TGF-β1 and α-SMA gene was verified by double luciferase target experiment.Results:Compared with blank control group, the expression level of nephrin in high glucose group and negative control group was significantly lower ( F=444.404, P<0.05). The relative expression of miRNA-192 increased while that of WT1 protein and mRNA decreased ( F=184.216, 243.543, 107.898, all P<0.05). WT1 was the target gene of miRNA-192 according to the analysis of double luciferase reporter gene. Compared with blank control group, the expression levels of TGF-β1, α-SMA protein and mRNA in high glucose group and negative control group were increased ( FTGF-β1 protein=69.014, P<0.05; Fα-SMA protein =87.644, P<0.05; FTGF-β1 mRNA=147.714, Fα-SMA mRNA=247.584, all P<0.05). Compared with negative control group, the expression level of nephrin in miRNA-192 inhibition group was increased ( t=16.519, P<0.05), the relative expression of miRNA-192 was decreased, and the relative expression of WT1 protein and mRNA were increased ( tmiRNA-192=10.533, tWT1=17.088, 8.186, all P<0.05). The expression levels of TGF-β1, α-SMA protein and mRNA protein were decreased ( tTGF-β1 protein=6.114, P<0.05; tα-SMA protein=7.941, P<0.05; tTGF-β1 mRNA=8.239, tα-SMA mRNA=8.481, P<0.05). Conclusion:miRNA-192 can promote the development of diabetic nephrophy by targetting WT1. Inhibition of miRNA-192 expression can reduce the EMT induced by high glucose in podocytes.

Objective To identify the significance of serum phospholipase A2 receptor antibody (PLA2R-Ab) in idiopathic membranous nephropathy (IMN) patients.Methods A total of 108 patients diagnosed as IMN by medical history,physical examination,laboratory examination and renal biopsy in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Dec 1,2014 and Aug 31,2017 were enrolled,and all related data were recorded.According to the results of serum PLA2R-Ab test,patients were divided to positive group and negative group,and the data were compared with the independent sample t test and the chi-square test.Kaplan-Meier survival analysis was performed to compare remission rates between groups,and the Logrank method was used to evaluate the significance of differences.Univariate and multivariate Cox regression analysis were used to verify predicting factors for achieving remission.Results Overall,67.6％(73/108) patients had detectable serum PLA2R-Ab.Compared with patients in negative group,patients in positive group exhibited higher proportion of male patients (P=0.002),lower level of serum albumin (P ＜ 0.001),higher level of cholesterol (P ＜ 0.001),lower level of immunoglobulin G (P ＜0.001),higher level of proteinuria (P=0.003),a lower of chance of remission (P=0.049),longer time needed to achieve partial remission (P=0.001) and complete remission (P=0.002).The 1-and 2-year cumulative renal partial remission rates were 72.4％,86.1％,and the cumulative renal complete remission rates were 43.8％,54.0％,respectively.Patients in negative group had higher partial remission (x2=9.84,P=0.002) and complete remission (x2=15.50,P＜0.001) than those in positive group.Multivariate Cox regression model indicated that serum positive PLA2R-Ab was a significant independent risk factor.Conclusions IMN patients with serum PLA2R-Ab show more severe condition and lower remission rates than those without serum PLA2R-Ab.Serum positive PLA2R-Ab is an independent remission-related predictor for IMN patients.

Weighted bidirected graph is an accurate representation for the problems in science and engineering that have linking relationships.Cluster detection on weighted bidirected graphs is an important research topic.This paper proposes an approach to detecting clusters from weighted bidirected graphs.Based on the definitions of adjusted weight and adjusted degree,this approach measures the structural similarity between nodes accurately,making full use of the weights and direction information of bidirected edges.Therefore,this approach detects clusters from weighted bidirected graphs well.The results of the comparative experiments show that the clusters detected by this approach have better quality than those detected by the comparative approach.