1. Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis
- Author
-
Bollee, Guillaume, Flamant, Martin, Schordan, Sandra, Fligny, Cecile, Rumpel, Elisabeth, Milon, Marine, Schordan, Eric, Sabaa, Nathalie, Vandermeersch, Sophie, Galaup, Ariane, Rodenas, Anita, Casal, Ibrahim, Sunnarborg, Susan W., Salant, David J., Kopp, Jeffrey B., Threadgill, David W., Quaggin, Susan E., Dussaule, Jean-Claude, Germain, Stephane, Mesnard, Laurent, Endlich, Karlhans, Boucheix, Claude, Belenfant, Xavier, Callard, Patrice, Endlich, Nicole, and Tharaux, Pierre-Louis
- Subjects
Glomerulonephritis -- Risk factors -- Diagnosis -- Care and treatment -- Research ,Biological sciences ,Health - Abstract
Rapidly progressive glomerulonephritis (RPGN) is a life-threatening clinical syndrome and a morphological manifestation of severe glomerular injury that is marked by a proliferative histological pattern ('crescents') with accumulation of T cells and macrophages and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the epidermal growth factor receptor (EGFR, also known as ErbBl) in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfrgene from podocytes of mice alleviates the severity of RPGN. Likewise, pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 d after the induction of experimental RPGN. This suggests that targeting the HB-EGF-EGFR pathway could also be beneficial in treatment of human RPGN., RPGN or crescentic glomerulonephritis is a life-threatening disease that destroys kidneys over a period of days to weeks. Proliferation of epithelial cells and infiltration of inflammatory cells lead to glomerular [...]
- Published
- 2011
- Full Text
- View/download PDF