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Epidermal growth factor: a new therapeutic target in glomerular disease.
MedLine Citation:
PMID:  22467748     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Glomerular kidney diseases are of major public health importance because of their strong impact on the quality of life of patients and of their costly management. A relatively neglected area of study is the local factors that influence development of glomerular demolition. The involvement of a glomerular factor has been now demonstrated in glomerulonephritis with cell proliferation such as crescentic rapidly progressive glomerulonephritis (RPGN). Various unrelated immune disorders promote RPGN, such as antibodies directed against the glomerular basement membrane, deposition of immune complexes or antibodies directed against neutrophils. Despite the heterogeneity of these causing diseases, RPGNs share similar histopathological features, which suggest involvement of common final pathways. De novo expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in glomerular epithelial cells is found specifically in human glomerulonephritis with proliferation of these cells and dedifferentiation of podocytes. A receptor for HB-EGF, the EGF receptor (EGFR), is expressed by parietal epithelial cells and podocytes. Furthermore, in a mouse model of RPGN, HB-EGF deficiency or conditional targeting of the Egfr alleles in podocytes markedly alleviated RPGN, renal failure and death. This indicates that the HB-EGF/EGFR pathway plays a pivotal role in RPGN and opens therapeutic perspectives as EGFR inhibitors are clinically available.
Authors:
Martin Flamant; Guillaume Bollée; Carole Hénique; Pierre-Louis Tharaux
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  27     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  1297-304     Citation Subset:  IM    
Affiliation:
Correspondence and offprint requests to: Pierre-Louis Tharaux; E-mail: pierre-louis.tharaux@inserm.fr.
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