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.

Epac‐Rap1‐activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction

“…N‐cadherin‐mediated junctions are of great importance in connective tissue physiology and are critical for the regulation of cell attachment and migration . N‐cadherin directs cell‐cell communication during mesenchymal condensation, a process mediated by surface contact that results in the aggregation of progenitor cells . Connexin‐43, a gap junction protein, is upregulated during cardiomyogenic differentiation of stem cells and is important for electric impulse generation in cardiac cells .…”

Prospective isolation of resident adult human mesenchymal stem cell population from multiple organs

“…SCRG1/BST1 preserves self-renewal potential and the expression of stem cell markers such as LNGFR, THY-1 and VCAM-1 [58]. Cell-cell adhesion in human MSCs enhances the expression of VCAM-1 via PDGFRb [59]. Based on a study of BM-MSCs, we found that LNGFR and THY-1 markers can be used to effectively isolate these cells from other tissues.…”

Effects of histone deacetylase inhibitors on regenerative cell responses in human dental pulp cells

“…The expression of VCAM‐1 was enhanced via PDGFRβ and the activation of Src in a ligand‐independent manner during the cell–cell adhesion process in MSCs (Aomatsu et al . ). Specific beta1 integrins mediate adhesion, migration and differentiation of neural progenitors derived from the embryonic striatum (Tate et al .…”

“…The intercellular adhesion molecule 1 (ICAM-1) can mediate the adherence process between mesenchymal stem cells (MSCs) and endothelial progenitor cells (Guo et al 2016). The expression of VCAM-1 was enhanced via PDGFRb and the activation of Src in a ligand-independent manner during the cell-cell adhesion process in MSCs (Aomatsu et al 2014). Specific beta1 integrins mediate adhesion, migration and differentiation of neural progenitors derived from the embryonic striatum (Tate et al 2004).…”