Angiotensin II increases fibronectin and collagen I through the β-catenin-dependent signaling in mouse collecting duct cells

Catherina A. Cuevas, ALEXIS ANTONIO GONZALEZ PARRA, Nibaldo C. Inestrosa, Carlos P. Vio, Minolfa C. Prieto

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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/β-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 β-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 β-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 β-catenin degradation with pyrvinium pamoate (pyr; 10–9 M) prevented the ANG II-induced expression of fibronectin, collagen I, and β-catenin target genes. ANG II treatment promoted the accumulation of β-catenin protein in a time-dependent manner. Because phosphorylation of glycogen synthase kinase-3β (GSK-3β) inhibits β-catenin degradation, we further evaluated the effects of ANG II and ANG II plus pyr on p-ser9-GSK-3β levels. ANG II-dependent upregulation of β-catenin protein levels was correlated with GSK-3β phosphorylation. These effects were prevented by pyr. Our data indicate that in M-1 collecting duct cells, the β-catenin pathway mediates the stimulation of fibronectin and collagen I in response to AT1 receptor activation.

Original languageEnglish
Pages (from-to)F358-F365
JournalAmerican Journal of Physiology - Renal Physiology
Volume308
Issue number4
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Mouse collecting duct cell
  • Pyrvinium pamoate
  • Tissue homeostasis

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