Stromal cell‐derived factor‐1α induces astrocyte proliferation through the activation of extracellular signal‐regulated kinases 1/2 pathway
- 1 June 2001
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 77 (5), 1226-1236
- https://doi.org/10.1046/j.1471-4159.2001.00350.x
Abstract
Stromal cell-derived factor-1 (SDF-1), the ligand of the CXCR4 receptor, is a chemokine involved in chemotaxis and brain development that also acts as co-receptor for HIV-1 infection. We previously demonstrated that CXCR4 and SDF-1α are expressed in cultured type-I cortical rat astrocytes, cortical neurones and cerebellar granule cells. Here, we investigated the possible functions of CXCR4 expressed in rat type-I cortical astrocytes and demonstrated that SDF-1α stimulated the proliferation of these cells in vitro. The proliferative activity induced by SDF-1α in astrocytes was reduced by PD98059, indicating the involvement of extracellular signal-regulated kinases (ERK1/2) in the astrocyte proliferation induced by CXCR4 stimulation. This observation was further confirmed showing that SDF-1α treatment selectively activated ERK1/2, but not p38 or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). Moreover, both astrocyte proliferation and ERK1/2 phosphorylation, induced by SDF-1α, were inhibited by pertussis toxin (PTX) and wortmannin treatment indicating the involvement of a PTX sensitive G-protein and of phosphatidyl inositol-3 kinase in the signalling of SDF-1α. In addition, Pyk2 activation represent an upstream components for the CXCR4 signalling to ERK1/2 in astrocytes. To our knowledge, this is the first report demonstrating a proliferative effect for SDF-1α in primary cultures of rat type-I astrocytes, and showing that the activation of ERK1/2 is responsible for this effect. These data suggest that CXCR4/SDF-1 should play an important role in physiological and pathological glial proliferation, such as brain development, reactive gliosis and brain tumour formation.Keywords
This publication has 59 references indexed in Scilit:
- Molecular characterization of CXCR–4: A potential brain tumor-associated geneJournal of Surgical Oncology, 1998
- The α-Chemokine, Stromal Cell-derived Factor-1α, Binds to the Transmembrane G-protein-coupled CXCR-4 Receptor and Activates Multiple Signal Transduction PathwaysJournal of Biological Chemistry, 1998
- Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar developmentNature, 1998
- The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tractNature, 1998
- The Chemokine SDF-1 Is a Chemoattractant for Human CD34+ Hematopoietic Progenitor Cells and Provides a New Mechanism to Explain the Mobilization of CD34+ Progenitors to Peripheral BloodThe Journal of Experimental Medicine, 1997
- The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1Nature, 1996
- The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entryNature, 1996
- Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1Nature, 1996
- Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.The Journal of cell biology, 1980
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976