Adducins are cytoskeletal actin-binding proteins (α, β, γ) that function as heterodimers and heterotetramers and are encoded by distinct genes. Experimental and clinical evidence implicates α- and β-adducin variants in hypertension and renal dysfunction. Here, we have addressed the role of α- and β-adducin on glomerular function and disease using β-adducin null mice, congenic substrains for α- and β-adducin from the Milan hypertensive (MHS) and Milan normotensive (MNS) rats and patients with IgA nephropathy. Targeted deletion of β-adducin in mice reduced urinary protein excretion, preceded by an increase of podocyte protein expression (phospho-nephrin, synaptopodin, α-actinin, ZO-1, Fyn). The introgression of polymorphic MHS β-adducin locus into MNS (Add2, 529R) rats was associated with an early reduction of podocyte protein expression (nephrin, synaptopodin, α-actinin, ZO-1, podocin, Fyn), followed by severe glomerular and interstitial lesions and increased urinary protein excretion. These alterations were markedly attenuated when the polymorphic MHS α-adducin locus was also present (Add1, 316Y). In patients with IgA nephropathy, the rate of decline of renal function over time was associated to polymorphic β-adducin (ADD2, 1797T, rs4984) with a significant interaction with α-adducin (ADD1, 460W, rs4961). These findings suggest that adducin genetic variants participate in the development of glomerular lesions by modulating the expression of specific podocyte proteins.
α- and β-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathy / M. Ferrandi, D.M. Cusi, I. Molinari, L. Del Vecchio, M.C. Barlassina, M.P. Rastaldi, F.P. Schena, F. Macciardi, C. Marcantoni, D. Roccatello, L.L. Peters, S. Armelloni, L. Min, L.A.E. Giardino, D. Mattinzoli, C. Camisasca, F. Palazzo, P. Manunta, P. Ferrari, G. Bianchi. - In: JOURNAL OF MOLECULAR MEDICINE. - ISSN 0946-2716. - 88:2(2010 Feb), pp. 203-217.
|Titolo:||α- and β-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathy|
CUSI, DANIELE MARIA (Secondo)
FERRARI, PATRIZIA (Penultimo)
|Parole Chiave:||Adducin; Genetic renal disease; Glomerular disease; IgA nephropathy; Podocytes; Proteinuria|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||feb-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s00109-009-0549-x|
|Appare nelle tipologie:||01 - Articolo su periodico|