Novel evidence demonstrates that epithelial-mesenchymal transition contributes to nephrolithiasis-induced renal fibrosis
Novel evidence demonstrates that epithelial-mesenchymal transition contributes to nephrolithiasis-induced renal fibrosis
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新证据表明上皮间质转化有助于肾结石引起的肾纤维化
DOI：
10.1016/j.jss.2012.07.066
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发表时间：
2013-06-01
影响因子：
2.2
通讯作者：
Zheng, Jun-Hua
中科院分区：
文献类型：
--
作者：
Liu, Min;Liu, Yong-Zhen;Zheng, Jun-Hua
目的：为探讨肾结石患者肾组织中纤维化病变的发生情况，选择性研究Twist和E-cadherin在肾结石患者肾组织中的表达及其临床意义。我们测定了血浆肌酐（Cr）和校正的Cr清除率（CCr）。对50例患者进行每日尿蛋白定量测定。在经皮肾镜取石术结束时，我们进行穿刺活检以获取肾脏组织。我们从开放手术中接受手术活检的非肾结石患者中获得正常对照肾组织。我们通过免疫组化染色测定Twist和E-cadherin的表达，并将其与临床参数进行评分。此外，我们分析了Twist的表达程度及其与长期肾survival.Results的相关性：总体而言，患者的肾功能显着下降，如所示的Cr和减少CCr与健康对照组相比。肾结石患者的肾小管上皮细胞中强烈表达激活的Twist，而我们在正常肾脏中几乎没有发现Twist的阳性染色。肾结石患者肾组织中E-cadherin的表达明显受到抑制。Twist表达与E-cadherin表达呈负相关;使用多变量分析，数据显示影响患者肾存活率的因素是CCr（相对比值，4.39; 95%置信区间，1.34-14.38; P = 0.013）和Twist表达程度结论：新的EMT标志物分子Twist和Twist染色可能是预测肾结石患者肾纤维化进展的一个有价值的指标。(C)2013 Elsevier Inc. All rights reserved.
Purpose: To investigate fibrotic lesions in renal tissues obtained from patients with large calculi, and to selectively evaluate the expression and clinical significance of Twist and E-cadherin in nephrolithiasis patients.Methods: We recruited 50 patients with kidney stone and 32 matched healthy controls. We determined plasma creatinine (Cr) and corrected Cr clearance (CCr). For the 50 patients, we detected daily urine protein excretion. At the end of percutaneous nephroscopic lithotomy, we performed puncture biopsy to acquire kidney tissue. We obtained normal control kidney tissues from non-nephrolithiasis patients who received a surgical biopsy during open surgery. We determined the expression of Twist and E-cadherin by immunohistochemical staining and scored it with clinical parameters. In addition, we analyzed the degree of expression of Twist and its correlation with long-term renal survival.Results: Overall, the renal function of patients significantly decreased, as indicated by Cr and reduced CCr compared with healthy controls. Activated Twist was strongly expressed in tubular epithelial cells from kidneys of nephrolithiasis patients, whereas we found little positive staining of Twist in normal kidneys. Meanwhile, the expression of E-cadherin was significantly suppressed in kidneys of nephrolithiasis patients. Twist expression was inversely correlated with E-cadherin expression; using multivariate analysis, data showed that the factors influencing renal survival in patients were CCr (relative ratio, 4.39; 95% confidence interval, 1.34-14.38; P = 0.013) and the extent of Twist expression (relative ratio, 3.45; 95% confidence interval, 1.10-10.68; P = 0.033).Conclusions: Our data suggest that the possible novel EMT marker molecule Twist and Twist staining might be a valuable index predicting renal fibrosis progression in human nephrolithiasis. (C) 2013 Elsevier Inc. All rights reserved.