Angiotensin II increases fibronectin and collagen I through the ß-catenin-dependent signaling in mouse collecting duct cells.
Am J Physiol Renal Physiol
; 308(4): F358-65, 2015 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-25411386
ABSTRACT
The contribution of angiotensin II (ANG II) to renal and tubular fibrosis has been widely reported. Recent studies have shown that collecting duct cells can undergo mesenchymal transition suggesting that collecting duct cells are involved in interstitial fibrosis. The Wnt/ß-catenin signaling pathway plays an essential role in development, organogenesis, and tissue homeostasis; however, the dysregulation of this pathway has been linked to fibrosis. In this study, we investigated whether AT1 receptor activation induces the expression of fibronectin and collagen I via the ß-catenin pathway in mouse collecting duct cell line M-1. ANG II (10(-7) M) treatment in M-1 cells increased mRNA, protein levels of fibronectin and collagen I, the ß-catenin target genes (cyclin D1 and c-myc), and the myofibroblast phenotype. These effects were prevented by candesartan, an AT1 receptor blocker. Inhibition of the ß-catenin degradation with pyrvinium pamoate (pyr; 10(-9) M) prevented the ANG II-induced expression of fibronectin, collagen I, and ß-catenin target genes. ANG II treatment promoted the accumulation of ß-catenin protein in a time-dependent manner. Because phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) inhibits ß-catenin degradation, we further evaluated the effects of ANG II and ANG II plus pyr on p-ser9-GSK-3ß levels. ANG II-dependent upregulation of ß-catenin protein levels was correlated with GSK-3ß phosphorylation. These effects were prevented by pyr. Our data indicate that in M-1 collecting duct cells, the ß-catenin pathway mediates the stimulation of fibronectin and collagen I in response to AT1 receptor activation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
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Transdução de Sinais
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Fibronectinas
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Colágeno Tipo I
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Beta Catenina
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Túbulos Renais Coletores
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article