UCH-L1 expression of podocytes in diseased glomeruli and in vitro
UCH-L1 expression of podocytes in diseased glomeruli and in vitro
复制标题
病变肾小球足细胞及体外 UCH-L1 表达
DOI：
10.1002/path.2511
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发表时间：
2009-04-01
影响因子：
7.3
通讯作者：
Zhang, Zhigang
中科院分区：
文献类型：
--
作者：
Liu, Yuan;Wu, Jiajing;Zhang, Zhigang
泛素c端水解酶- l1 （Ubiquitin C-terminal hydroase - l1, UCH-L1）是泛素-蛋白酶体途径中去泛素化酶家族的重要成员，主要表达于神经系统和生殖系统以及一些肿瘤中。最近，UCH-L1在肾包曼囊壁上皮细胞和部分肾小管上皮中被发现表达。然而，UCH-L1是否在肾小球毛细血管簇中表达尚不清楚。本研究采用免疫组织化学、双免疫荧光标记、肾活检组织免疫电镜和western blot对培养的大鼠足细胞进行UCH-L1的表达及调控。结果显示UCH-L1在足细胞中表达，且在急性增生性肾小球肾炎（APGN）、狼疮性肾炎（LN）、膜性肾小球肾炎（MGN）和IgA肾病中的表达明显高于局灶节段性肾小球硬化（FSGS）、微小病变（MCD）、轻微异常和正常肾组织中的表达（p < 0.05）。体外实验中，western blot结果显示，两组足细胞与系膜细胞共培养，分别暴露于ATS 50 μ l/ml、ATS 50 μ l/ml与正常人血清30 μ l/ml时，UCH-L1表达显著升高（p < 0.05），而TGF β 1 1 ng/ml、TNF α 10 ng/ml或IL-1 10 ng/ml处理组UCH-L1表达几乎不升高，与正常对照比较，差异无统计学意义（p < 0.05）。进一步检查发现，LN、APGN和IgA肾病中pcna阳性足细胞的比例显著高于MCD、FSGS和正常对照组（p < 0.05）。这些数据首次表明足细胞确实表达UCH-L1，并且在这些免疫复合物介导的肾组织中UCH-L1的表达可以增加。免疫损伤是刺激足细胞表达UCH-L1的主要原因。UCH-L1的表达可能与足细胞的再生有关，作为免疫复合物介导的损伤的修复反应。版权所有2008年英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
Ubiquitin C-terminal hydrolase-L1 (UCH-L1), an important member of de-ubiquitination enzyme families involved in the ubiquitin-proteasome pathway, is expressed mainly in neural and reproductive systems as well as in some tumours. Recently, expression of UCH-L1 has been discovered in parietal epithelial cells of Bowman's capsules and some tubular epithelia in the kidney. However, whether UCH-L1 is expressed in the capillary tufts of the glomeruli has not yet become clear. In this study, we used immunohistochemistry, double immunofluorescence labelling, immunoelectron microscopy in kidney biopsy tissues and western blot in cultured rat podocytes to investigate the expression of UCH-L1 and the regulation of this expression in podocytes. The results demonstrated that UCH-L1 was expressed in podocytes and its expression was significantly higher in acute proliferative glomerulonephritis (APGN), lupus nephritis (LN), membranous glomerulonephritis (MGN) and IgA nephropathy than that in focal segmental glomeruloselerosis (FSGS), minimal change disease (MCD), minor abnormality and normal kidney tissues (p < 0.05). In in vitro experiments, western blot showed that UCH-L1 expression significantly increased in the two groups of podocytes co-cultured with mesangial cells exposed to ATS 50 mu l/ml and ATS 50 mu l/ml with normal human serum 30 mu l/ml, respectively (p < 0.05), while the other groups treated with TGF beta 1 1 ng/ml, TNF alpha 10 ng/ml or IL-1 10 ng/ml had little rise of UCH-L1 expression, with no statistical significance compared with normal control (P > 0.05). Further tests indicated that the percentage of PCNA-positive podocytes in LN, APGN and IgA nephropathy was significantly higher than that in MCD, FSGS and normal control (p < 0.05). These data show for the first time that podocytes do express UCH-L1 and that its expression can be increased in these immunocomplex-mediated nephrites. The immune injury is a main cause for stimulating podocytes to express UCH-L1. The expression of UCH-L1 may be associated with the regeneration of podocytes as a repair response to immunocomplex-mediated injury. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.