Altered Expression of Nephrin, Glomerular Epithelial Cell Protein-1 (GLEPP1) and WT-1 in Glomerular Disease

ABSTRACT

BACKGROUND: Glomerular epithelial cell protein-1 (GLEPP1) and WT-1 expressed in mature visceral glomerular epithelial cell (VGEC) is required for maintenance of the mature status of VGEC. Nephrin protein is located at the filtration slit and regarded as a molecular component of the slit diaphragm. Alterations of these proteins in proteinuric diseases are not clearly defined. METHODS: We investigated the expression of GLEPP1, WT-1 and nephrin in 28 renal biopsies diagnosed with minimal change nephropathy (n=10), focal glomerulosclerosis (n=10) and membranous nephritis (n=8) by immunohistochemical staining. Normal control biopsies were obtained from six nephrectomy specimens. RESULTS: The patients consisted of 15 males and 13 females. The mean age was 40.7 years. Nephrotic range proteinuria (> or =3.5 g/day) was noted in 15 (54%) patients. GLEPP1 and nephrin expression were significantly decreased in patients as compared with those of the controls (p<0.05). The mean number of WT-1 expressing cells per glomerulus was also significantly decreased in patients as compared with those of the controls (p<0.05). However, there was no significant difference in the number of WT-1 expressing cells among the disease groups. CONCLUSIONS: These results suggest that the loss of biological markers of mature VGEC may play an important role in the pathogenesis of proteinuria.