Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1α in MSCs

摘要: Recent evidence indicated that sublethal hypoxic preconditioning (HP) of bone marrow-derived mesenchymal stem cells (MSCs) before transplantation could ameliorate their capacity to survive and engraft in the target tissue through yet undefined mechanisms. In this study, we demonstrated HP (3% oxygen) induced high expression both chemokine stromal-derived factor-1 (SDF-1) receptors, CXCR4 CXCR7, MSCs. also improved vitro migration, adhesion survival Although SDF-1-induced migration HP-MSCs was only abolished by an anti-CXCR4 antibody, CXCR7 were responsible for elevated HP-MSCs. Moreover, but not essential resistance oxidative stress HP-MSC. addition, evoked increase hypoxia-inducible (HIF-1α) phosphorylation Akt. The chemical inducers HIF-1α, desferrioxamine (DFX) cobalt chloride (CoCl 2 ), upregulation MSCs under normoxic conditions. Contrarily, blockade HIF-1α siRNA inhibition Akt either wortmannin or LY294002 abrogated HP-induced Collectively, these findings provide a crucial role PI3K/Akt-HIF-1α-CXCR4/CXCR7 pathway on enhanced vitro.