title: ARS-interacting multi-functional protein 1 induces proliferation of human bone marrow-derived mesenchymal stem cells by accumulation of β-catenin via fibroblast growth factor receptor 2-mediated activation of Akt.
abstract: ARS-Interacting Multi-functional Protein 1 (AIMP1) is a cytokine that is involved in the regulation of angiogenesis, immune activation, and fibroblast proliferation. In this study, fibroblast growth factor receptor 2 (FGFR2) was isolated as a binding partner of AIMP peptide (amino acids 6-46) in affinity purification using human bone marrow-derived mesenchymal stem cells (BMMSCs). AIMP1 peptide induced the proliferation of adult BMMSCs by activating Akt, inhibiting glycogen synthase kinase-3β, and thereby increasing the level of β-catenin. In addition, AIMP1 peptide induced the translocation of β-catenin to the nucleus and increased the transcription of c-myc and cyclin D1 by activating the β-catenin/T-cell factor (TCF) complex. By contrast, transfection of dominant negative TCF abolished the effect of AIMP1. The inhibition of Akt, using LY294002, abolished the accumulation and nuclear translocation of β-catenin induced by AIMP1, leading to a decrease in c-myc and cyclin D1 expression, which decreased the proliferation of BMMSCs. An intraperitoneal injection of AIMP1 peptide into C57/BL6 mice increased the colony formation of fibroblast-like cells. Fluorescence activated cell sorting analysis showed that the colony-forming cells were CD29(+)/CD44(+)/CD90(+)/CD105(+)/CD34(-)/CD45(-), which is characteristic of MSCs. In addition, the fibroblast-like cells differentiated into adipocytes, chondrocytes, and osteocytes. Taken together, these data suggest that AIMP1 peptide promotes the proliferation of BMMSCs by activating the β-catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in MSCs in peripheral blood.
authors.affiliation: 1 Laboratory for Tracing of Gene Function, Department of Biomedical Science, CHA University , Sungnam-si, Korea.
authors.forename: Seo Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Son
authors.forename: Min Chul
authors.initials: MC
authors.lastname: Park
authors.forename: Chul Min
authors.initials: CM
authors.lastname: Kim
authors.forename: Byung Hyun
authors.initials: BH
authors.lastname: Cha
authors.forename: Kang Jun
authors.initials: KJ
authors.lastname: Yoon
authors.forename: Soo-Hong
authors.initials: SH
authors.lastname: Lee
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Park
mesh_terms: D021581:Active Transport, Cell Nucleus; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; D002867:Chromones; D016207:Cytokines; C489427:MYC protein, human; D009025:Morpholines; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D051820:TCF Transcription Factors; D051176:beta Catenin; C077219:small inducible cytokine subfamily E, member 1; D019938:Cyclin D1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3