RGD Reference Report - Prevention of renal vascular and glomerular fibrosis by epidermal growth factor receptor inhibition. - Rat Genome Database

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Prevention of renal vascular and glomerular fibrosis by epidermal growth factor receptor inhibition.

Authors: Francois, H  Placier, S  Flamant, M  Tharaux, PL  Chansel, D  Dussaule, JC  Chatziantoniou, C 
Citation: Francois H, etal., FASEB J. 2004 May;18(7):926-8. Epub 2004 Mar 19.
RGD ID: 1581909
Pubmed: PMID:15033924   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.03-0702fje   (Journal Full-text)

Hypertension is frequently associated with the development of renal vascular and glomerular fibrosis. The purpose of the present study was to investigate whether epidermal growth factor receptor (EGFR) activation participates in the development of renal fibrosis and to test if blockade of EGFR activation would have therapeutic effects. Experiments were performed during nitric oxide (NO) deficiency-induced hypertension in rats (L-NAME model). After 4 weeks of L-NAME treatment, animals developed hypertension associated to deterioration of renal structure and function. Over the same period, EGFR was activated twofold within glomeruli. This activation was accompanied by increased activity of the mitogen-activated protein kinase (MAPK) p42/p44 pathway and exaggerated collagen I expression. Gefitinib, an EGFR-tyrosine kinase inhibitor, given concomitantly with L-NAME, normalized MAPK activation and collagen I expression and prevented the decline of renal function and the development of fibrosis. Since endothelin mediates the L-NAME-induced fibrogenesis, the endothelin-EGFR interaction was tested in transgenic mice expressing luciferase under the control of collagen I-alpha2 promoter: In renal cortex of these animals, the endothelin-induced collagen I gene activity was inhibited by an EGFR-phosphorylation inhibitor. These results provide the first evidence that EGFR activation plays an important role in the progression of renal vascular and glomerular fibrosis.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal fibrosis  IDA 1581909 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)


Additional Information