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Expression and functional role of formyl peptide receptor in human bone marrow-derived mesenchymal stem cells
Authors:Kim Mi-Kyoung  Min Do Sik  Park Yoon Jeong  Kim Jae Ho  Ryu Sung Ho  Bae Yoe-Sik
Affiliation:Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
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.
Keywords: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
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