Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach
Author: ["Alexandre Lautrette","Shunqiang Li","Rohia Alili","Susan W Sunnarborg","Martine Burtin","David C Lee","Gérard Friedlander","Fabiola Terzi"]
Publication: Nature Medicine
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Abstract
Mechanisms of progression of chronic renal diseases, a major healthcare burden, are poorly understood. Angiotensin II (AngII), the major renin-angiotensin system effector, is known to be involved in renal deterioration, but the molecular pathways are still unknown. Here, we show that mice overexpressing a dominant negative isoform of epidermal growth factor receptor (EGFR) were protected from renal lesions during chronic AngII infusion. Transforming growth factor-α (TGF-α) and its sheddase, TACE (also known as ADAM17), were induced by AngII treatment, TACE was redistributed to apical membranes and EGFR was phosphorylated. AngII-induced lesions were substantially reduced in mice lacking TGF-α or in mice given a specific TACE inhibitor. Pharmacologic inhibition of AngII prevented TGF-α and TACE accumulation as well as renal lesions after nephron reduction. These findings indicate a crucial role for AngII-dependent EGFR transactivation in renal deterioration and identify in TACE inhibitors a new therapeutic strategy for preventing progression of chronic renal diseases.
Cite this article
Lautrette, A., Li, S., Alili, R. et al. Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach. Nat Med 11, 867–874 (2005). https://doi.org/10.1038/nm1275
