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NDT Advance Access originally published online on April 18, 2007
Nephrology Dialysis Transplantation 2007 22(7):1903-1909; doi:10.1093/ndt/gfm135
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Expression of filtrin in human glomerular diseases

Pekka Ihalmo1,2, Holger Schmid3, Maria Pia Rastaldi4, Deborah Mattinzoli4, Robyn G. Langham5, Pauliina Luimula1, Riika Kilpikari2, Markus Lassila1, Richard E. Gilbert5,6, Dontscho Kerjaschki7, Matthias Kretzler3,8 and Harry Holthöfer1

1Department of Bacteriology and Immunology, Haartman Institute, 2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland, 3Medizinische Poliklinik, Ludwig-Maximillians-University of Munich, Munich, Germany, 4Renal Immunopathology Laboratory, Fondazione D’Amico per la Ricerca sulle Malattie Renali, San Carlo Borromeo Hospital, Milan, Italy, 5Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Australia, 6Department of Medicine, University of Toronto, St. Michael's Hospital, Toronto, Canada, 7Institute of Clinical Pathology, University of Vienna, Allgemeines Krankenhaus, Vienna, Austria and 8Division of Nephrology, University of Michigan Medical Center, Ann Arbor, MI, USA

Correspondence and offprint requests to: Harry Holthöfer, MD, PhD. Email: harry.holthofer{at}helsinki.fi



  Abstract

Background. Filtrin (NEPH3/KIRREL2) is a recently characterized member of the nephrin-like proteins of the immunoglobulin superfamily, and it has been suggested to participate in the maintenance of the glomerular filtration barrier in the kidney. In this study, the gene and protein expression of filtrin were examined in patients with acquired proteinuric diseases.

Methods. Filtrin mRNA levels in renal biopsies were measured with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in two sets of patients with proteinuria. The mRNA levels were normalized to the housekeeping gene GAPDH and also related to the podocyte-specific genes nephrin and podocin. Immunofluorescence microscopy was employed to explore changes in the glomerular distribution of filtrin.

Results. Reduced glomerular expression of filtrin mRNA was observed in all studied diagnostic groups. In focal segmental glomerulosclerosis, the filtrin mRNA level was only one-tenth of the control samples (P {approx} 5.0 x 10–6), and this finding was confirmed in a second set of samples. The ratios of filtrin to nephrin and podocin demonstrated a marked decrease in the expression of filtrin relative to the podocyte marker genes. However, no correlation between the expression of filtrin and the levels of serum creatinine and proteinuria was observed. Immunostaining showed changes in the expression pattern of filtrin in renal biopsies. Immunoelectron microscopic studies localized filtrin at the slit diaphragm of the podocyte foot processes.

Conclusions. Down-regulation of the filtrin gene and protein expression in the renal biopsies together with the localization to the inter-podocyte filtration slit imply a potential role for this molecule in the pathogenesis of proteinuric diseases.

Keywords: gene expression; glomerulus; kidney biopsy; podocyte; proteinuria

Received for publication: 16. 8.06
Accepted in revised form: 16. 2.07


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