title: Epidermal growth factor: a new therapeutic target in glomerular disease.
abstract: 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.affiliation: Service de Physiologie-Explorations Fonctionnelles, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, and Paris Cardiovascular Centre, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Flamant
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bollée
authors.forename: Carole
authors.initials: C
authors.lastname: Hénique
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Tharaux
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005921:Glomerulonephritis / Q000188:drug therapy*; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000503:physiopathology*; D051379:Mice
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors