Extracellular TGF-β downregulates the expression of Wnt transcription factor TCF7L2/TCF4 in mesenchymal stromal cells and fibroblasts

摘要: Mesenchymal stromal cells (MSCs) are multipotent progenitors essential for organogenesis, tissue homeostasis, regeneration, and scar formation. Tissue injury upregulates TGF-β signaling, which plays predominant roles in MSCs fate, extracellular matrix (ECM) remodeling, fibrogenesis. However, the molecular determinants of differentiation survival still poorly understood. The canonical Wnt Tcf/Lef transcription factors important players development stem cell but mechanisms by injury-induced signaling cues regulate expression remain Here, we studied cell-specific gene and, more specifically, investigated whether damage-induced affects function TCF7L2 using different vitro models MSCs, including fibro-adipogenic progenitors. We demonstrated that members differentially expressed impairs these not myoblasts. Also, show ubiquitin-proteasome system (UPS) regulates proteostasis participates TGF-β-mediated protein downregulation. Finally, also requires HDACs activity to repress fibroblasts. Thus, our work establishes a novel interplay between cascades suggests this mechanism could be targeted fibrosis.