β-Arrestin-1 deficiency ameliorates renal interstitial fibrosis by blocking Wnt1/β-catenin signaling in mice

In this study, we identified for the first time that β-arrest in-1 was upregulated in the kidney from mice with unilateral ureteral obstruction nephropathy as well as in the paraffin-embedded sections of human kidneys from the patients with diabetic nephropathy, polycystic kidney, or uronephrosis, which normally causes renal fibrosis. Deficiency of β-arrestin -1 in mice significantly alleviated renal fibrosis by the regulation of inflammatory responses, kidney fibroblast activation, and epithelial-mesenchymal transition (EMT) in both in vivo and in vitro studies. Furthermore, we found that among the major isoforms of Wnts, Wnt1 was regulated by β-arrest in-1 and gene silencing of Wnt1 inhibited the activation of β-catenin and suppressed β-arrestin-1-mediated renal fibrosis. Collectively, our results indicate that β-arrestin-1 is one of the critical components of signal transduction pathways in the development of renal fibrosis. Modulation of the se pathways may be an innovative therapeutic strategy for treating patients with renal fibrosis.Key messagesβ-Arrestin-1 was upregulated in the kidney from mice with UUO nephropathy.β-Arrestin-1 regulated kidney fibroblast activation and epithelial-mesenchymal transition.β-Arrestin-1 exacerbated renal fibrosis via mediating Wnt1/β-catenin signaling.

Source: Journal of Molecular Medicine - November 7, 2017 Category: Molecular Biology Source Type: research