2. Academic Validation
  3. Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis

Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis

  • Nat Med. 2011 Sep 25;17(10):1242-50. doi: 10.1038/nm.2491.
Guillaume Bollée 1,  Martin Flamant,  Sandra Schordan,  Cécile Fligny,  Elisabeth Rumpel,  Marine Milon,  Eric Schordan,  Nathalie Sabaa,  Sophie Vandermeersch,  Ariane Galaup,  Anita Rodenas,  Ibrahim Casal,  Susan W Sunnarborg,  David J Salant,  Jeffrey B Kopp,  David W Threadgill,  Susan E Quaggin,  Jean-Claude Dussaule,  Stéphane Germain,  Laurent Mesnard,  Karlhans Endlich,  Claude Boucheix,  Xavier Belenfant,  Patrice Callard,  Nicole Endlich,  Pierre-Louis Tharaux
Affiliations

Affiliation

  • 1 Unité Mixte de Recherche (UMR) 970, Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
PMID: 21946538 DOI: 10.1038/nm.2491
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 ErbB1) 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 EGFR gene 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.

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