title: Et and diabetic nephropathy: preclinical and clinical studies.
abstract: The incidence of progressive kidney disease associated with diabetes continues to increase worldwide. Only partial renoprotection is achieved by current standard therapy with angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers, increasing the need for novel therapeutic approaches. Experimental studies have provided evidence of a pathogenic role for endothelin-1 (ET-1) and its cognate receptors in the development and progression of diabetic nephropathy. ET-1, mainly through the activation of ETA receptor, contributes to renal cell injury, inflammation, and fibrosis. In animal models of type 1 and type 2 diabetes, ETA-selective antagonists have been shown to provide renoprotective effects, supplying the rationale for clinical trials in patients with diabetic nephropathy with ETA-receptor antagonists administered in addition to renin-angiotensin system blockade.
authors.affiliation: Unit of Advanced Microscopy, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gagliardini
authors.affiliation: Laboratory of Pathophysiology of Experimental Renal Disease and Interaction With Other Organ Systems, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors.forename: Carlamaria
authors.initials: C
authors.lastname: Zoja
authors.affiliation: Department of Molecular Medicine, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy. Electronic address: ariela.benigni@marionegri.it.
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D016232:Endothelins / Q000378:metabolism*; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans
chemical_list: D016232:Endothelins
keywords: Diabetic nephropathy; dual inhibition of endothelin-converting enzyme; endothelin-receptor antagonists; neutral endopeptidase; renin-angiotensin system inhibitors