title: Involvement of the tubular ClC-type exchanger ClC-5 in glomeruli of human proteinuric nephropathies.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine, Nephrology Unit and Kidney Histomorphology and Molecular Biology Laboratory, University of Padova, Padova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ceol
authors.forename: Emilia
authors.initials: E
authors.lastname: Tiralongo
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Baelde
authors.forename: Daniela
authors.initials: D
authors.lastname: Vianello
authors.forename: Giovanni
authors.initials: G
authors.lastname: Betto
authors.forename: Annunziata
authors.initials: A
authors.lastname: Marangelli
authors.forename: Luciana
authors.initials: L
authors.lastname: Bonfante
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.forename: Mila
authors.initials: M
authors.lastname: Della Barbera
authors.forename: Angela
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Franca
authors.initials: F
authors.lastname: Anglani
authors.forename: Dorella
authors.initials: D
authors.lastname: Del Prete
mesh_terms: D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D012333:RNA, Messenger