Expression and functional role of formyl peptide receptor in human bone marrow-derived mesenchymal stem cells

Abstract 

We investigated the expression of formyl peptide receptor (FPR) and its functional role in human bone marrow-derived mesenchymal stem cells (MSCs). We analyzed the expression of FPR by using ligand-binding assay with radio-labeled N-formyl-met-leu-phe (fMLF), and found that MSCs express FPR. FMLF stimulated intracellular calcium increase, mitogen-activated protein kinases activation, and Akt activation, which were mediated by G_i proteins. MSCs were chemotactically migrated to fMLF. FMLF-induced MSC chemotaxis was also completely inhibited by pertussis toxin, LY294002, and PD98059, indicating the role of G_i proteins, phosphoinositide 3-kinase, and extracellular signal regulated protein kinase. N-terminal fragment of annexin-1, Anx-1(2–26), an endogenous agonist for FPR, also induced chemotactic migration of MSCs. Thus MSCs express functional FPR, suggesting a new (patho)physiological role of FPR and its ligands in regulating MSC trafficking during induction of injured tissue repair.

Abbreviations: MSCs, mesenchymal stem cells, FPR, formyl peptide receptor, fMLF, N-formyl-met-leu-phe, CsH, cyclosporine H, PTX, pertussis toxin, LY294002, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, Fura-2/AM, fura-2 pentaacetoxymethylester, BAPTA/AM, 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl) ester, ERK, extracellular signal regulated protein kinase, PD98059, 2′-amino-3′-methoxyflavone, SB203580, 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole, [Ca²⁺]_i, intracellular calcium concentration, MAPK, mitogen-activated protein kinase, PI3K, phosphoinositide 3-kinase

Keywords: Mesenchymal stem cells, Formyl peptide receptor, Chemotaxis, fMLF, Annexin-1, Pertussis toxin-sensitive G-protein