MicroRNA-26a Participation the wnt/β-catenin Signaling Pathway Induced Renal Fibrosis by Target GSK-3β in IgA Nephropathy / 现代生物医学进展

ABSTRACT

Objective:Through detecting miRNA-26a,β-catenin,GSK-3β and α-SMA expressions in IgA nephropathy with varying degrees of renal interstitial fibrosis,the study was performed to explore the effect of miRNA-26a targeting GSK-3β on Wnt/β-catenin signal pathway simulated renal interstitial fibrosis.Methods:Incorporated 46 cases of IgA nephropathy patients were divided into three group based on the degree of renal interstitial fibrosis,namely,mild group,moderate group and severe group;7 cases of normal renal tissues away from the renal tumor tissues were selected as the control group.Expression levels of miRNA-26a in renal tissues of each group were detected based on RT-qPCR method,to analyze the correlation between miRNA-26a and renal fibrosis In patients with IgA nephropathy.Furthermore,mRNA and protein expression levels of β-catenin,GSK-3β and α-SMA in renal tissues were measured using RT-qPCR and immunohistochemistry,respectively,the comparison was then made in each group;subsequently,correlation analysis was further conducted to investigate the relationship of miRNA-26a with β-catenin,GSK-3β and α-SMA.Results:(1) Compared with the control group,miRNA-26a expression was down-regulated from renal biopsy of IgA nephropathy patients,the expression level of miRNA-26a was significantly decreased,showing statistical differences among groups (P＜0.05).(2) Compared with the control group,mRNA and protein expression levels of β-catenin,GSK-3β and α-SMA in renal tissues were all increased in IgA nephropathy patients,and the degree of expression increased gradually with the increase of the degree of renal interstitial lesion,differences were statistically significant among groups (P＜0.05).(3) Correlation analysis results indicated that there were negative correlation between miRNA-26a expression in renal tissues and the degree of renal interstitial fibrosis,differences were statistically significant among groups (r=-0.943,P ＜0.05),at the same time,expression intensities of GSK-3β,β-catenin and α-SMA in renal interstitium and renal tubules were positively correlated with the degree of renal interstitial fibrosis(r =0.917,P＜0.05;r =0.943,P＜0.05;r =0.926,P ＜0.05),meanwhile,positive correlation was also found regarding protein expression of GSK-3β and β-catenin in renal interstitium (r=0.834,P＜0.05).Conclusion:Collectively,miRNA-26a can be involved in Wnt/β-catenin signal pathway simulated renal interstitial fibrosis via the regulation of GSK-3β.