Stromal cell-derived factor-1α induces astrocyte proliferation through the activation of extracellular signal-regulated kinases 1/2 pathway

摘要: Stromal cell-derived factor-1 (SDF-1), the ligand of CXCR4 receptor, is a chemokine involved in chemotaxis and brain development that also acts as co-receptor for HIV-1 infection. We previously demonstrated SDF-1alpha are expressed cultured type-I cortical rat astrocytes, neurones cerebellar granule cells. Here, we investigated possible functions astrocytes stimulated proliferation these cells vitro. The proliferative activity induced by was reduced PD98059, indicating involvement extracellular signal-regulated kinases (ERK1/2) astrocyte stimulation. This observation further confirmed showing treatment selectively activated ERK1/2, but not p38 or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). Moreover, both ERK1/2 phosphorylation, SDF-1alpha, were inhibited pertussis toxin (PTX) wortmannin PTX sensitive G-protein phosphatidyl inositol-3 signalling SDF-1alpha. In addition, Pyk2 activation represent an upstream components to astrocytes. To our knowledge, this first report demonstrating effect primary cultures responsible effect. These data suggest CXCR4/SDF-1 should play important role physiological pathological glial proliferation, such development, reactive gliosis tumour formation.