title: Cell-cell adhesion through N-cadherin enhances VCAM-1 expression via PDGFRβ in a ligand-independent manner in mesenchymal stem cells.
abstract: Cell-cell adhesions induce various intracellular signals through hierarchical and synergistic molecular interactions. Recently, we demonstrated that a high cell density induces the expression of vascular cell adhesion molecule-1 (VCAM-1) through the nuclear factor-κB (NF-κB) pathway in human bone marrow-derived mesenchymal stem cells (MSCs). However, the specific molecules that activated the NF-κB pathway were not determined. In the present study, in experiments with receptor tyrosine kinase inhibitors, VCAM-1 expression was completely suppressed by platelet-derived growth factor (PDGF) receptor (PDGFR) inhibitors. In addition, VCAM-1 expression was significantly suppressed by knockdown with PDGFRβ siRNA, but not with PDGFRα siRNA. However, VCAM-1 expression did not increase following treatment with PDGF. The overexpression of N-cadherin, a structural molecule in adherence junctions in MSCs, promoted VCAM-1 expression and induced the marked phosphorylation of the intracellular signaling factor, Src. In addition, VCAM-1 expression and Src phosphorylation were reduced by the overexpression of a dominant negative mutant of N-cadherin. These results suggest that cell-cell adhesion, through N-cadherin, enhances the expression of VCAM-1 via PDGFRβ and the activation of Src in a ligand-independent manner in MSCs.
authors.affiliation: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Aomatsu
authors.affiliation: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Chosa
authors.affiliation: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan.
authors.forename: Soko
authors.initials: S
authors.lastname: Nishihira
authors.affiliation: Division of Oral Surgery, Department of Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miura
authors.affiliation: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishisaki
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008024:Ligands; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D015820:Cadherins; D008024:Ligands; D019010:Vascular Cell Adhesion Molecule-1; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt