ARS-Interacting Multi-Functional Protein 1 Induces Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Accumulation of beta-Catenin via Fibroblast Growth Factor Receptor 2-Mediated Activation of Akt

作者：Kim Seo Yoon; Son Woo Sung; Park Min Chul; Kim Chul Min; Cha Byung Hyun; Yoon Kang Jun; Lee Soo Hong; Park Sang Gyu^*

来源：Stem Cells and Development, 2013, 22(19): 2630-2640.

DOI：10.1089/scd.2012.0714

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-3, and thereby increasing the level of -catenin. In addition, AIMP1 peptide induced the translocation of -catenin to the nucleus and increased the transcription of c-myc and cyclin D1 by activating the -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 -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 -catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in MSCs in peripheral blood.

• 出版日期2013-10-1