Wnt4/β-catenin信号通路在肾小球疾病中的表达及其临床意义

    Expression and clinical significance of Wnt4/β-catenin signaling pathway in glomerular diseases

    • 摘要: 目的 初步探讨原发性肾小球肾炎肾组织中wnt4、β-catenin的表达与肾小管损伤及肾间质纤维化的关系。方法 收集明确诊断为原发性肾小球肾炎并行肾穿刺活检患者56例为研究对象,根据肾小管间质损伤评分分为轻度损伤组(n=22)、中度损伤组(n=18)、重度损伤组(n=16),另外选取10例正常肾组织(均来自于肾肿瘤患者切除肾脏的远端正常肾组织)作为正常对照组。采用免疫组化检测肾组织中wnt4、β-catenin表达水平,同时测定相关的临床指标,分析wnt4、β-catenin的水平变化与患者的临床特点的关系。结果 免疫组化显示,wnt4、β-catenin在正常对照组肾组织中无明显表达,而在原发性肾小球肾炎患者肾组织中表达明显,随着肾间质纤维化的程度,wnt4、β-catenin蛋白表达呈递增趋势(P<0.05)。wnt4在肾小管上皮细胞中的表达强度与β2微球蛋白(r=0.29,P<0.05)呈正相关性,与eGFR (r=-0.38,P<0.05)呈负相关性。结论 wnt4、β-catenin在肾间质纤维化的原发性肾小球肾炎患者肾组织中的表达水平一致,均高于未发生纤维化的正常肾组织,wnt4/β-catenin信号通路可能参与原发性肾小球肾炎肾小管间质纤维化进程。

       

      Abstract: Objective To preliminarily investigate the relationship between the expression of wnt4 and β-catenin in the renal glomerulonephritis tissue and renal tubular injury and renal interstitial fibrosis. Methods A total of 56 patients with primary glomerulonephritis and renal biopsy were enrolled in the study. According to tubulointerstitial injury scores, the patients were divided into mild injury group (n=22), moderate injury group (n=18) and severe injury group (n=16), and another 10 patients with normal renal tissues (all from excised normal renal tissues of patients with renal tumor) were chosen as the control group. Immunohistochemistry was used to detect wnt4 and β-catenin in renal tissues in each group. The related clinical indicators were determined at the same time to analyze the relationship between the changes of wnt4 and β-catenin levels and clinical characteristics of the patients. Results Immunohistochemistry showed that, wnt4 and β-catenin were not expressed in renal tissues in the normal control group, but were notably expressed in renal tissues of patients with glomerulonephritis. With the severity of renal interstitial fibrosis, the expression levels of wnt4 and β-catenin exhibited an increasing trend (P<0.05). The expression level of wnt4 in epithelial cells in the renal tubules exhibited positive correlation with β2-microglobin (r=0.29, P<0.05), and negative correlation with eGFR (r=-0.38, P<0.05). Conclusions The expression levels of wnt4 and β-catenin in renal tissue of patients with primary glomerulonephritis with renal interstitial fibrosis are consistent, are both higher than those in normal renal tissue without fibrosis. The wnt4/β-catenin signaling pathway may be involved in the progression of tubulointerstitial fibrosis in glomerulonephritis.

       

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