Contreras, Osvaldo and Soliman, Hesham and Theret, Marine and Rossi, Fabio M. V. and Brandan, Enrique (2020) TGF-β-driven downregulation of the Wnt/β-Catenin transcription factor TCF7L2/TCF4 in PDGFRα+ fibroblasts. Journal of Cell Science. pp. jcs.242297. ISSN 0021-9533
Full text not available from this repository.Abstract
Mesenchymal stromal/stem cells (MSCs) are multipotent progenitors essential for organogenesis, tissue homeostasis, regeneration, and scar formation. Tissue injury upregulates TGF-β signaling, which modulates myofibroblast fate, extracellular matrix remodeling, and fibrosis. However, the molecular determinants of MSCs differentiation and survival remain poorly understood. The canonical Wnt Tcf/Lef transcription factors regulate development and stemness, but the mechanisms by which injury-induced cues modulate their expression remain underexplored. Here, we studied the cell-specific gene expression of Tcf/Lef and, more specifically, we investigated whether damage-induced TGF-β impairs the expression and function of TCF7L2, using several models of MSCs, including skeletal muscle fibro-adipogenic progenitors. We show that Tcf/Lefs are differentially expressed and that TGF-β reduces the expression of TCF7L2 in MSCs but not in myoblasts. We also found that the ubiquitin-proteasome system regulates TCF7L2 proteostasis and participates in TGF-β-mediated TCF7L2 protein downregulation. Finally, we show that TGF-β requires HDACs activity to repress the expression of TCF7L2. Thus, our work found a novel interplay between TGF-β and Wnt canonical signaling cascades in PDGFRα+ fibroblasts and suggests that this mechanism could be targeted in tissue repair and regeneration.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 02 Jun 2020 03:28 |
| Last Modified: | 02 Jun 2020 03:28 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/973 |
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