Proteolytic processed form of CXCL12 abolishes migration and induces apoptosis in neural stem cells in vitro

Autor(es)

Adelita, Tais ; Stilhano, Roberta Sessa ; Han, SangWon ; Justo, Giselle Zenker ; Porcionatto, Marimelia

• Tipo de documento: Artigo Científico
• Fonte: STEM CELL RESEARCH; v. 22, p. 61-69, JUL 2017.
• Citações Web of Science: 5

Resumo

The subventricular zone (SVZ) of the adult mammalian brain hosts full potential neural stem cells (NSCs). NSCs are able to respond to extracellular signals in the brain, amplifying the pool of progenitor cells and giving rise to neuroblasts that showability to migrate towards an injury site. These signals can come fromvascular system, cerebrospinal fluid, glial cells, or projections of neurons in adjoining regions. CXCL12, a chemokine secreted after brain injury, reaches the SVZ in a gradient manner and drives neuroblasts towards the lesion area. Among many other molecules, matrix metalloproteinase 2 and 9 (MMP-2/9) are also released during brain injury. MMP-2/9 can cleave CXCL12 generating a new molecule, CXCL12(5-67), and its effects on NSCs viability is not well described. Here we produced recombinant CXCL12 and CXCL12(5-67) and evaluated their effect inmurine adultNSCsmigration and survival in vitro. We showed CXCL12(5-67) does not promote NSCsmigration, but does induce cell death. The NSC death induced by CXCL12(5-67) involves caspases 9 and 3/7 activation, implying the intrinsic apoptotic pathway in this phenomenon. Our evidences in vitromake CXCL12(5-67) and its receptor potential candidates for brain injuries and neurodegeneration studies. (C) 2017 The Author(s). Published by Elsevier B.V. (AU)

• Processo FAPESP: 11/11388-4 - Estudo dos efeitos da quimiocina CXCL12 na sobrevivência e diferenciação de neuroblastos derivados de células tronco neurais
• Beneficiário: Taís Adelita Morais de Almeida
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/19231-8 - Crosstalk entre as vias Wnt, SHH e Notch na aquisição de fenótipo de célula-tronco por astrócitos reativos
• Beneficiário: Marimélia Aparecida Porcionatto
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/00652-5 - Estudo dos mecanismos moleculares da migração, sobrevivência e diferenciação de células-tronco neurais
• Beneficiário: Marimélia Aparecida Porcionatto
• Linha de fomento: Auxílio à Pesquisa - Regular