Upregulation of CXCR4 favoring neural-like cells migration via AKT activation.
Stromal cell-derived factor-1alpha (SDF-1alpha) and its chemokine receptor 4 (CXCR4) play an important role in regulating bone marrow stromal stem cells (BMSCs) migration, proliferation and differentiation. The aim of this study is to investigate the expression of CXCR4 receptor and related mechanisms involved in neural-like cells migration. Results demonstrated that BMSCs were successfully induced to differentiate into neural-like cells, as early as 6h after the initiation of neural differentiation, as revealed by both RT-PCR and immunocytochemistry. Interestingly, neuronal induction media (NIM) increased CXCR4 expression via Akt activation, which resulted in the increased ability of migration toward SDF-1alpha in neural-like cells. Furthermore, we showed that migration toward SDF-1 was attenuated by AMD3100 (specific inhibitor of CXCR4) and Phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These data suggest that the PI3K/Akt signaling pathway activated by NIM enhances migration of neural-like cells toward SDF-1alpha though upregulation of CXCR4. This finding presents opportunities to develop new therapeutic strategies for the treatment of CNS disorders.
Li
Shiyong
S
Key Laboratory of Molecular Medicine, Second Affiliated Hospital of Nanchang University, Nanchang City, China.
Deng
Liying
L
Gong
Limin
L
Bian
Hetao
H
Dai
Yucheng
Y
Wang
Ye
Y
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000502:physiology; D003470:Culture Media / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D054377:Chemokine CXCL12; D003470:Culture Media; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt