Open AccessInvolvement of the Tubular ClC-Type Exchanger ClC-5 in Glomeruli of Human Proteinuric Nephropathies
Author(s) -
Monica Ceol,
Emilia Tiralongo,
Hans J. Baelde,
Daniela Vianello,
Giovanni Betto,
A. Marangelli,
Luciana Bonfante,
Marialuisa Valente,
Mila Della Barbera,
Angela D’Angelo,
Franca Anglani,
Dorella Del Prete
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0045605
Subject(s) - podocyte , proteinuria , immunohistochemistry , endocytosis , diabetic nephropathy , pathology , glomerulopathy , glomerulonephritis , albuminuria , nephrotic syndrome , kidney , renal biopsy , nephropathy , medicine , endocrinology , biopsy , chemistry , diabetes mellitus , receptor
Glomerular protein handling mechanisms have received much attention in studies of nephrotic syndrome. Histopathological findings in renal biopsies from severely proteinuric patients support the likelihood of protein endocytosis by podocytes. ClC-5 is involved in the endocytosis of albumin in the proximal tubule. Aim To investigate whether ClC-5 is expressed in the glomerular compartment and whether it has a role in proteinuric nephropathies. ClC-5 expression was studied using Real-time PCR in manually- and laser-microdissected biopsies from patients with type 2 diabetes (n 37) and IgA nephropathy (n 10); in biopsies of membranous glomerulopathy (MG) (n 14) immunohistochemistry for ClC-5 (with morphometric analysis) and for WT1 was done. Controls: cortical tissue (n 23) obtained from unaffected parts of tumor-related nephrectomy specimens. Results ClC-5 was expressed at glomerular level in all biopsies. Glomerular ClC-5 levels were significantly higher in diabetic nephropaty and MG at both mRNA and protein level (p<0.002; p<0.01). ClC-5 and WT1 double-staining analysis in MG showed that ClC-5 was localized in the podocytes. ClC-5 ultrastructural immunolocalization was demonstrated in podocytes foot processes. Our study is the first to demonstrate that ClC-5 is expressed in human podocytes. The ClC-5 overexpression found in biopsies of proteinuric patients suggests that proteinuria may play a part in its expression and that podocytes are likely to have a key role in albumin handling in proteinuric states.