Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis
Friedrich-Alexander-Universität Erlangen-Nürnberg · University of Michigan–Ann Arbor · +1 more institution
Abstract
The transforming growth factor-β (TGF-β) signalling pathway is a key mediator of fibroblast activation that drives the aberrant synthesis of extracellular matrix in fibrotic diseases. Here we demonstrate a novel link between transforming growth factor-β and the canonical Wnt pathway. TGF-β stimulates canonical Wnt signalling in a p38-dependent manner by decreasing the expression of the Wnt antagonist Dickkopf-1. Tissue samples from human fibrotic diseases show enhanced expression of Wnt proteins and decreased expression of Dickkopf-1. Activation of the canonical Wnt pathway stimulates fibroblasts in vitro and induces fibrosis in vivo. Transgenic overexpression of Dickkopf-1 ameliorates skin fibrosis induced by…
Citation impact
- FWCI
- 22.84
- Percentile
- 100%
- References
- 61
Authors
17- AAAlfiya AkhmetshinaCorresponding
Friedrich-Alexander-Universität Erlangen-Nürnberg
- KPKatrin Palumbo
Friedrich-Alexander-Universität Erlangen-Nürnberg
- CDClara Dees
Friedrich-Alexander-Universität Erlangen-Nürnberg
- CBChristina Bergmann
Friedrich-Alexander-Universität Erlangen-Nürnberg
- PVPaulius Venalis
Friedrich-Alexander-Universität Erlangen-Nürnberg
Topics & keywords
- Wnt signaling pathway
- LRP5
- Transforming growth factor
- Fibrosis
- Cell biology
- LRP6
- Signal transduction
- Cancer research