CXCL12 N-terminal end is sufficient to induce chemotaxis and proliferation of neural stem/progenitor cells

Autor(es)

Filippo, Thais R. M. ^[1] ; Galindo, Layla T. ^{[2, 1]} ; Barnabe, Gabriela F. ^[3] ; Ariza, Carolina B. ^[1] ; Mello, Luiz E. ^{[2, 3]} ; Juliano, Maria A. ^[4] ; Juliano, Luiz ^[4] ; Porcionatto, Marimelia A. ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biochem, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Neurobiol Lab, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Physiol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: STEM CELL RESEARCH; v. 11, n. 2, p. 913-925, SEP 2013.
• Citações Web of Science: 24

Resumo

Neural stem/progenitor cells (NSC) respond to injury after brain injuries secreting IL-1, IL-6, TNF-alpha, IL-4 and IL-10, as well as chemokine members of the CC and CXC ligand families. CXCL12 is one of the chemokines secreted at an injury site and is known to attract NSC-derived neuroblasts, cells that express CXCL12 receptor, CXCR4. Activation of CXCR4 by CXCL12 depends on two domains located at the N-terminal of the chemokine. In the present work we aimed to investigate if the N-terminal end of CXCL12, where CXCR4 binding and activation domains are located, was sufficient to induce NSC-derived neuroblast chemotaxis. Our data show that a synthetic peptide analogous to the first 21 amino acids of the N-terminal end of CXCL12, named PepC-C (KPVSLSYRCPCRFFESHIARA), is able to promote chemotaxis of neuroblasts in vivo, and stimulate chemotaxis and proliferation of CXCR4+ cells in vitro, without affecting NSC fate. We also show that PepC-C upregulates CXCL12 expression in vivo and in vitro. We suggest the N-terminal end of CXCL12 is responsible for a positive feedback loop to maintain a gradient of CXCL12 that attracts neuroblasts from the subventricular zone into an injury site. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 12/00652-5 - Estudo dos mecanismos moleculares da migração, sobrevivência e diferenciação de células-tronco neurais
• Beneficiário: Marimélia Aparecida Porcionatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 05/04061-8 - Terapia celular aplicada a regeneração de lesões no sistema nervoso central: transplante de células-tronco da medula óssea expressando condroitinase AC
• Beneficiário: Marimélia Aparecida Porcionatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular