title: Astrocytes treated by lysophosphatidic acid induce axonal outgrowth of cortical progenitors through extracellular matrix protein and epidermal growth factor signaling pathway.
abstract: Lysophosphatidic acid (LPA) plays important roles in many biological processes, such as brain development, oncogenesis and immune functions, via its specific receptors. We previously demonstrated that LPA-primed astrocytes induce neuronal commitment of cerebral cortical progenitors (Spohr et al. 2008). In the present study, we analyzed neurite outgrowth induced by LPA-treated astrocytes and the molecular mechanism underlying this event. LPA-primed astrocytes increase neuronal differentiation, arborization and neurite outgrowth of developing cortical neurons. Treatment of astrocytes with epidermal growth factor (EGF) ligands yielded similar results, suggesting that members of the EGF family might mediate LPA-induced neuritogenesis. Furthermore, treatment of astrocytes with LPA or EGF ligands led to an increase in the levels of the extracellular matrix molecule, laminin (LN), thus enhancing astrocyte permissiveness to neurite outgrowth. This event was reversed by pharmacological inhibitors of the MAPK signaling pathway and of the EGF receptor. Our data reveal an important role of astrocytes and EGF receptor ligands pathway as mediators of bioactive lipids action in brain development, and implicate the LN and MAPK pathway in this process.
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21949-590 RJ, Brazil.
authors.forename: Tania Cristina Leite de Sampaio
authors.initials: TC
authors.lastname: E Spohr
authors.forename: Rômulo Sperduto
authors.initials: RS
authors.lastname: Dezonne
authors.forename: Stevens Kastrup
authors.initials: SK
authors.lastname: Rehen
authors.forename: Flávia Carvalho Alcantara
authors.initials: FC
authors.lastname: Gomes
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001369:Axons / Q000187:drug effects*; D015153:Blotting, Western; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D007797:Laminin / Q000502:physiology; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D016501:Neurites / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D007797:Laminin; D008246:Lysophospholipids; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; C032881:lysophosphatidic acid