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PMID: 16543220 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells.

Genes & development ·Vol. 20 ·No. 6 ·2006-03-15 ·Pages 666-74

Jian H, Shen X, Liu I, Semenov M, He X, Wang XF

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 beta1 (TGF-beta1) and Wnt signaling pathways in regulating the activities of human MSCs. We show that TGF-beta1 induces rapid nuclear translocation of beta-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 differentiation by TGF-beta1, likely through the regulation of specific downstream target genes. These results provide evidence for a new mode of cooperation between the TGF-beta 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.

MeSH Terms
Base Sequence Bone Marrow Cells/cytology Cell Nucleus/metabolism Cell Proliferation DNA Primers Humans Mesenchymal Stem Cells/cytology Protein Transport Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Smad3 Protein/physiology Transforming Growth Factor beta/physiology Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
DNA Primers SMAD3 protein, human Smad3 Protein Transforming Growth Factor beta Wnt Proteins beta Catenin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Jian Hongyan
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Shen Xing
Liu Irwin
Semenov Mikhail
He Xi
Wang Xiao-Fan
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2006-03-15
Pages
666-74
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1413283
Subset
IM
Grants
NIDDK NIH HHS · R01 DK064113 · United States
NIDDK NIH HHS · DK064113 · United States
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