| First Author | Ryu JM | Year | 2015 |
| Journal | Stem Cells | Volume | 33 |
| Issue | 3 | Pages | 819-32 |
| PubMed ID | 25376707 | Mgi Jnum | J:223670 |
| Mgi Id | MGI:5660057 | Doi | 10.1002/stem.1882 |
| Citation | Ryu JM, et al. (2015) Autotaxin-LPA axis regulates hMSC migration by adherent junction disruption and cytoskeletal rearrangement via LPAR1/3-dependent PKC/GSK3beta/beta-catenin and PKC/Rho GTPase pathways. Stem Cells 33(3):819-32 |
| abstractText | Bioactive molecules and stem cell-based regenerative engineering is emerging a promising approach for regenerating tissues. Autotaxin (ATX) is a key enzyme that regulates lysophosphatidic acid (LPA) levels in biological fluids, which exerts a wide range of cellular functions. However, the biological role of ATX in human umbilical cord blood-derived mesenchymal stem cells (hMSCs) migration remains to be fully elucidated. In this study, we observed that hMSCs, which were stimulated with LPA, accelerated wound healing, and LPA increased the migration of hMSCs into a wound site in a mouse skin wound healing model. In an experiment to investigate the effect of LPA on hMSC migration, ATX and LPA increased hMSC migration in a dose-dependent manner, and LPA receptor 1/3 siRNA transfections inhibited the ATX-induced cell migration. Furthermore, LPA increased Ca(2+) influx and PKC phosphorylation, which were blocked by Galphai and Galphaq knockdown as well as by Ptx pretreatment. LPA increased GSK3beta phosphorylation and beta-catenin activation. LPA induced the cytosol to nuclear translocation of beta-catenin, which was inhibited by PKC inhibitors. LPA stimulated the binding of beta-catenin on the E-box located in the promoter of the CDH-1 gene and decreased CDH-1 promoter activity. In addition, the ATX and LPA-induced increase in hMSC migration was blocked by beta-catenin siRNA transfection. LPA-induced PKC phosphorylation is also involved in Rac1 and CDC42 activation, and Rac1 and CDC42 knockdown abolished LPA-induced F-actin reorganization. In conclusion, ATX/LPA stimulates the migration of hMSCs through LPAR1/3-dependent E-cadherin reduction and cytoskeletal rearrangement via PKC/GSK3beta/beta-catenin and PKC/Rho GTPase pathways. |
