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J Pathol. 2009 Apr;217(5):642-53. doi: 10.1002/path.2511.

UCH-L1 expression of podocytes in diseased glomeruli and in vitro.

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Department of Pathology and Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.


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 glomerulosclerosis (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 microl/ml and ATS 50 microl/ml with normal human serum 30 microl/ml, respectively (p < 0.05), while the other groups treated with TGFbeta1 1 ng/ml, TNFalpha 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.

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