Smad3-dependent nuclear translocation of β-catenin is required for TGF-β1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells
Open Access
- 15 March 2006
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 20 (6) , 666-674
- https://doi.org/10.1101/gad.1388806
Abstract
Adult mesenchymal stem cells (MSCs) derived from bone marrow contribute to the regeneration of multiple types of mesenchymal tissues. Here we describe the functional role of a novel form of cross-talk between the transforming growth factor β1 (TGF-β1) and Wnt signaling pathways in regulating the activities of human MSCs. We show that TGF-β1 induces rapid nuclear translocation of β-catenin in MSCs in a Smad3-dependent manner. Functionally, this pathway is required for the stimulation of MSC proliferation and the inhibition of MSC osteogenic differetiation by TGF-β1, likely through the regulation of specific downstream target genes. These results provide evidence for a new mode of cooperation between the TGF-β and Wnt signaling pathways in this specific cellular context and suggest a potentially important role for this distinct signaling pathway in the control of self-renewal and differentiation of a specific type of MSCs.Keywords
This publication has 28 references indexed in Scilit:
- Sequence-specific targeting of MSL complex regulates transcription of the roX RNA genesThe EMBO Journal, 2004
- Specific inhibition of gene expression using a stably integrated, inducible small‐interfering‐RNA vectorEMBO Reports, 2003
- Casein Kinase Iε Enhances the Binding of Dvl-1 to Frat-1 and Is Essential for Wnt-3a-induced Accumulation of β-CateninJournal of Biological Chemistry, 2003
- Axin Facilitates Smad3 Activation in the Transforming Growth Factor β Signaling PathwayMolecular and Cellular Biology, 2001
- Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-β and Wnt pathwaysProceedings of the National Academy of Sciences, 2000
- Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizerNature, 2000
- T cell factor-activated transcription is not sufficient to induce anchorage-independent growth of epithelial cells expressing mutant β-cateninProceedings of the National Academy of Sciences, 1999
- TGF-β–induced Phosphorylation of Smad3 Regulates Its Interaction with Coactivator p300/CREB-binding ProteinMolecular Biology of the Cell, 1998
- Transcriptional Activators of TGF-β Responses: SmadsCell, 1998
- Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation.Genes & Development, 1996