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

• Autor(a) principal: Adelita, Tais [UNIFESP]
• Data de Publicação: 2017
• Outros Autores: Stilhano, Roberta Sessa [UNIFESP], Han, SangWon [UNIFESP], Justo, Giselle Zenker [UNIFESP], Porcionatto, Marimelia [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1016/j.scr.2017.05.013; https://repositorio.unifesp.br/handle/11600/53576
• topic: CXCL12; CXCL12(5-67); Adult neural stem cell; Migration; Apoptosis; In vitro study

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.