Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies
Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies
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DOI：
10.1046/j.1523-1755.2002.00430.x
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发表时间：
2002-07-01
影响因子：
19.6
通讯作者：
D'Amico, G
中科院分区：
文献类型：
--
作者：
Rastaldi, MP;Ferrario, F;D'Amico, G
背景。在最近对培养细胞和实验性肾病进行的研究中。据推测，小管上皮细胞（TEC）可以通过上皮-间充质转化（EMT）成为胶原生成细胞。根据这一理论，它们应该经历几个激活步骤，如增殖和表型改变。最终合成细胞外基质（ECM）。评估EMT是否在人类tec中起作用。对133例不同肾脏疾病的肾活检组织进行了免疫组织化学和原位杂交，分析了增殖标志物（PCNA、mb -1）、细胞表型标志物（vimentin、α - sma、细胞角蛋白）的可能表达。ZO-1)和ECM的生成(脯氨酰4-羟化酶，HSP47；间质胶原蛋白).Results。独立于组织学诊断，PCNA（2.7 +/- 2.4细胞/场）和mb -1（1.9 +/- 2.3）存在不同程度的TEC阳性。同时检测到表达波形蛋白（1.4 +/- 4.7）和α -平滑肌肌动蛋白（α - sma; 0.04 +/-: 0.4）的tec。有可能观察到8 - 10%的管状截面上皮抗原的丢失。此外，TECs采用脯氨酸4-羟化酶（3.6 +/- 4.3）、热休克蛋白47 （HSP47: 2.9 +/- 5.4）、I型胶原（0.2 +/- 2.7）和III型胶原（0.3 +/- 2.0）染色。在0.8 ~ 1.4个细胞/场中发现I型和III型胶原mrna。具有EMT特征的TEC数量与血清肌酐和间质损害程度相关（P≤0.03），即使考虑到45例间质轻度病变，肾小管中所有标志物的表达仍与肾功能严格相关（P≤0.01）。我们的研究结果表明，通过过渡到间充质表型，TEC可以在人类疾病中产生ECM蛋白并直接干预纤维化过程。此外，EMT特征与血清肌酐的关联支持了这些标志物在评估疾病严重程度方面的价值。
Background. In recent studies performed on cultured cells and experimental nephropathies. it has been hypothesized that tubular epithelial cells (TEC), via epithelial-mesenchymal transformation (EMT), can become collagen-producing cells. According to this theory, they should proceed through several activating steps, such as proliferation and phenotype changes. to eventually synthesize extracellular matrix (ECM).Methods. To evaluate whether EMT operates in human TECs. 133 renal biopsies of different renal diseases were studied, analyzing by immunohistochemistry and in situ hybridization the possible expression of markers of proliferation (PCNA, Mib-1), cellular phenotype (vimentin, alpha-SMA, cytokeratin. ZO-1) and ECM production (prolyl 4-hydroxylase, HSP47. interstitial collagens).Results. Independently of histological diagnosis, variable degrees of TEC positivity for PCNA (2.7 +/- 2.4 cells/field) an Mib-1 (1.9 +/- 2.3) were present. TECs expressing vimentin (1.4 +/- 4.7) and alpha-smooth muscle actin (alpha-SMA; 0.04 +/-: 0.4) also were detected. It was possible to observe loss of epithelial antigens from 8 to 10% of the tubular cross sections. Moreover, TECs were stained by prolyl 4-hydroxylase (3.6 +/- 4.3), heat shock protein-47 (HSP47: 2.9 +/- 5.4), collagen type I (0.2 +/- 2.7) and type III (0.3 +/- 2.0). Collagen types I and III mRNAs were found in 0.8 to 1.4 cells/field. The number of TEC with EMT features were associated with serum creatinine and the degree of interstitial damage (P less than or equal to 0.03), and even considering the 45 cases with mild interstitial lesions, the tubular expression of all markers remained strictly associated with renal function (P less than or equal to 0.01).Conclusions. Our results suggest that, via transition to a mesenchymal phenotype, TEC can produce ECM proteins in human disease and directly intervene in the fibrotic processes. Moreover, the association of EMT features with serum creatinine supports the value of these markers in the assessment of disease severity.