Abstract 1022: Apolipoprotein-J Enhances CXCR4/SDF-Migration of Fetal Cardiac Myobalsts
A strong capacity of homing and traffic is critical for stem cells to enter and repair diseased organs and tissues. However, the mechanisms responsible for stem cell migration and homing remain largely unknown. Apolipoprotein-J (ApoJ), a stress-responding, chaperone-like protein in high-density lipoprotein, may exert a protective effect on stem cells against oxidative injury. Recently, we have shown that expression of ApoJ by cDNA transfection markedly reduces apoptosis in fetal cardiac myoblast, and restores the mitochondrial membrane potential and prevents the release of cytochrome C from mitochondria into cytoplasma. In this study, we further examined the role of ApoJ in cardiovascular progenitor gene expression. As determined by real-time PCR and by flow cytometry, ApoJ overexpression by cDNA transfection did not alter expression of c-kit, VEGFR2 and sca-1 but significantly increased expression of the chemokine receptor CXCR4 (receptor for stromal cell-derived factor-1, SDF-1). Moreover, Apo J markedly increased the migratory response of fetal cardiac myoblast to SDF-1 (Apo J compared to control 2.17 ± 0.08 fold increase, p<0.001) but not to VEGF (Apo J compared to control = 0.99 ± 0.02, p = NS). Incubation with anti-CXCR4 antibody (10 ug/ml) inhibited the migration of stem cell enhanced by ApoJ (ApoJ + CXCR4 antibody compared to control = 1.08 ± 0.04 fold). These data indicate that ApoJ increased stem cell migration is CXCR4 dependent. In addition, the ApoJ-induced increase in stem cell migration in response to SDF-1 was attenuated by PI3 kinase inhibitor LY294002 (0–5 uM) (ApoJ ± PI3 inhibitor compared to control = 1.02 ± 0.02 fold) but not by mitogen-activated protein/ERK kinase inhibitor PD98059 (0 –30 uM) (ApoJ ± MAP kinase inhibitor compared to control = 2.18 ± 0.18 fold increase, p<0.02). Our data indicate that Apo J increases stem cell migratory responses via CXCR4 chemokine receptor signaling which is PI3/Akt dependent. These findings provide a new paradigm for the biological role of ApoJ in regulation of stem cell functions and have implications for the development of a novel stem cell therapeutic strategy.