title: CXCL12 N-terminal end is sufficient to induce chemotaxis and proliferation of neural stem/progenitor cells.
abstract: Neural stem/progenitor cells (NSC) respond to injury after brain injuries secreting IL-1, IL-6, TNF-α, 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.
authors.affiliation: Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
authors.forename: Thais R M
authors.initials: TR
authors.lastname: Filippo
authors.forename: Layla T
authors.initials: LT
authors.lastname: Galindo
authors.forename: Gabriela F
authors.initials: GF
authors.lastname: Barnabe
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Ariza
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Mello
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.forename: Marimélia A
authors.initials: MA
authors.lastname: Porcionatto
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002531:Cerebellum / Q000166:cytology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse
keywords: NPC; NSC; SCI; SVZ; TBI; neural stem/progenitor cells; neuronal progenitor cells; spinal cord injury; subventricular zone; traumatic brain injury