RRC ID 56132
Author Dubon MJ, Yu J, Choi S, Park KS.
Title Transforming growth factor β induces bone marrow mesenchymal stem cell migration via noncanonical signals and N-cadherin.
Journal J Cell Physiol
Abstract Transforming growth factor-beta (TGF-β) induces the migration and mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF-β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration, and mobilization of BM-MSCs mediated by TGF-β are unclear. In this study, we showed that TGF-β activated noncanonical signaling molecules, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF-β type I receptor in human BM-MSCs and murine BM-MSC-like ST2 cells. Inhibition of Rac1 by NSC23766 and Src by PP2 resulted in impaired TGF-β-mediated migration. These results suggested that the Smad-independent, noncanonical signals activated by TGF-β were necessary for migration. We also showed that N-cadherin-dependent intercellular interactions were required for TGF-β-mediated migration using functional inhibition of N-cadherin with EDTA treatment and a neutralizing antibody (GC-4 antibody) or siRNA-mediated knockdown of N-cadherin. However, N-cadherin knockdown did not affect the global activation of noncanonical signals in response to TGF-β. Therefore, these results suggested that the migration of BM-MSCs in response to TGF-β was mediated through N-cadherin and noncanonical TGF-β signals.
Volume 233(1)
Pages 201-213
Published 2018-1-1
DOI 10.1002/jcp.25863
PMID 28213973
MeSH Animals Antigens, CD / genetics Antigens, CD / metabolism* Bone Marrow Cells / drug effects* Bone Marrow Cells / metabolism Cadherins / antagonists & inhibitors Cadherins / genetics Cadherins / metabolism* Cell Movement / drug effects* Cells, Cultured Extracellular Signal-Regulated MAP Kinases / metabolism Focal Adhesion Kinase 1 / metabolism Humans Mesenchymal Stem Cells / drug effects* Mesenchymal Stem Cells / metabolism Mice Neuropeptides / metabolism Protein Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism RNA Interference Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta / agonists Receptors, Transforming Growth Factor beta / metabolism Signal Transduction / drug effects* Transfection Transforming Growth Factor beta1 / pharmacology* p38 Mitogen-Activated Protein Kinases / metabolism rac1 GTP-Binding Protein / metabolism src-Family Kinases / metabolism
IF 4.522
Times Cited 16
Human and Animal Cells ST2(RCB0224)