title: Fibroblast growth factor-1-induced ERK1/2 signaling reciprocally regulates             proliferation and smooth muscle cell differentiation of ligament-derived endothelial             progenitor cell-like cells.
abstract: The periodontal ligament (PDL) is a fibrous connective tissue located between             the tooth root and the alveolar bone. We previously demonstrated that a single             cell-derived culture of primarily cultured PDL fibroblasts has the potential to             construct an endothelial cell (EC) marker-positive blood vessel-like structure,             suggesting that the fibroblastic lineage cells in ligament tissue could act as             the endothelial progenitor cells (EPCs), which regenerate to construct a vascular             system around the damaged ligament tissue. Moreover, we showed that EPC-like fibroblasts             expressed not only EC markers but also smooth muscle cell (SMC) markers. Generally,             an interaction between ECs and SMCs regulates blood vessel development and remodeling,             and is required for the formation of a mature and functional vascular network.             However, the mechanism underlying the SMC differentiation of the ligament-derived             EPC-like fibroblasts remains to be clarified. In this study, we showed that suppression             of fibroblast growth factor 1 (FGF-1)-induced extracellular signal-regulated kinase             1/2 (ERK1/2) signaling with the MAPK/ERK kinase (MEK) inhibitor U0126 completely             abolished the FGF-1-induced proliferation of the ligament-derived EPC-like fibroblasts.             In addition, U0126 treatment of FGF-1-stimulated ligament-derived EPC-like fibroblasts             significantly induced the SMC differentiation of the cells. Thus, FGF-1-induced             ERK1/2 signaling not only promoted the proliferation of the ligament-derived EPC-like             fibroblasts, but also suppressed the SMC differentiation of the cells, suggesting             that FGF-1 controls the construction of a vascular network around the ligament             tissue by regulating the proliferation and SMC differentiation of the EPC-like             cells through ERK-mediated signaling.
authors: Division of Cellular Biosignal Sciences, Department of Biochemistry,                     Iwate Medical University, Nishitokuta, Yahaba-cho, Iwate 028-3694, Japan.
authors: Mikako
authors: M
authors: Takahashi
authors: Naoto
authors: N
authors: Okubo
authors: Naoyuki
authors: N
authors: Chosa
authors: Noriko
authors: N
authors: Takahashi
authors: Miho
authors: M
authors: Ibi
authors: Masaharu
authors: M
authors: Kamo
authors: Harumi
authors: H
authors: Mizuki
authors: Akira
authors: A
authors: Ishisaki
authors: Seiko
authors: S
authors: Kyakumoto
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010513:Periodontal Ligament / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
chemical_list: D000199:Actins; D016220:Fibroblast Growth Factor 1; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3