miR-155调控Wnt/β-catenin信号通路与IgAN肾小管间质纤维化的关系

The Association of Wnt/β-catenin Signaling Pathway Regulated by miR-155 with Renal Interstitial Fibrosis in IgA Nephropathy

目的:检测miR^(-1)55在Ig A肾病(IgAN)中的表达,探讨其与患者临床病理参数的相关性及可能作用机制。方法:应用实时荧光定量PCR检测肾活检组织中miR^(-1)55的表达水平;利用脂质体介导miR^(-1)55 mimics瞬时转染人肾近曲小管上皮细胞(HK-2),通过RT-PCR和Western blot检测β-catenin、snail、fibronectin、E-cadherin的表达情况。结果:miR^(-1)55在IgAN组肾活检组织中的表达水平显著高于对照组(P<0.01);肾活检组织中miR^(-1)55表达量与肾小管间质纤维化呈正相关关系,与肾小球滤过率呈负相关关系;体外细胞实验显示,上调miR^(-1)55表达可激活Wnt/β-catenin信号通路,间质表型标志物fibronectin表达升高,而上皮表型标志物E-cadherin表达下降。结论:miR^(-1)55的表达上调与IgAN肾小管间质纤维化密切相关,其可能通过调控Wnt/β-catenin信号通路参与IgAN的进展。

Objective： To investigate the expression of miR-155 in patients with immunoglobulin A nephropathy（ IgAN）,and to analyze its role in renal interstitial fibrosis. Methods： The expression levels of miR-155 within kidney biopsies were assessed by real-time quantitative RT-PCR. miR-155 mimics were transiently transfected into human proximal tubule epithelial cells（ HK-2）. The expression of epithelial and mesenchymal markers as well as transcriptional regulators in Wnt/β-catenin signaling pathway were detected by RT-PCR and Western blotting. Results： Higher miR-155 expression was found in renal biopsy tissues from IgAN patients compared to controls（ P〈 0. 01）. The expression levels of miR-155 were positively correlated with renal interstitial fibrosis,but were inversely correlated with estimated glomerular filtration rate. Up-regulation of miR-155 induced the activation of the Wnt/β-catenin signaling pathway,which in turn increased fibronectin and reduced E-cadherin expression. Conclusion： miR-155 was elevated in IgAN patients,and the increased levels were correlated with the severity of renal interstitial fibrosis. This indicates that miR-155 may play a critical role in the pathogenesis of IgAN.