title: Fibulin-2 is a key mediator of the pro-neurogenic effect of TGF-beta1 on adult neural stem cells.
abstract: Transforming growth factor beta 1 (TGF-beta1), an anti-inflammatory cytokine, has been shown to have pro-neurogenic effects on adult Neural Stem Cells (aNSC) from the dentate gyrus and in vivo models. Here, we expanded the observation of the pro-neurogenic effect of TGF-beta1 on aNSC from the subventricular zone (SVZ) of adult rats and performed a functional genomic analysis to identify candidate genes to mediate its effect. 10 candidate genes were identified by microarray analysis and further validated by qRT-PCR. Of these, Fibulin-2 was increased 477-fold and its inhibition by siRNA blocks TGF-beta1 pro-neurogenic effect. Curiously, Fibulin-2 was not expressed by aNSC but by a GFAP-positive population in the culture, suggesting an indirect mechanism of action. TGF-beta1 also induced Fibulin-2 in the SVZ in vivo. Interestingly, 5 out of the 10 candidate genes identified are known to interact with integrins, paving the way for exploring their functional role in adult neurogenesis. In conclusion, we have identified 10 genes with putative pro-neurogenic effects, 5 of them related to integrins and provided proof that Fibulin-2 is a major mediator of the pro-neurogenic effects of TGF-beta1. These data should contribute to further exploring the molecular mechanism of adult neurogenesis of the genes identified and the involvement of the integrin pathway on adult neurogenesis.
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors.forename: Pablo Daniel
authors.initials: PD
authors.lastname: Radice
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mathieu
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors.forename: María Celeste
authors.initials: MC
authors.lastname: Leal
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Farías
authors.affiliation: Italian Hospital, Juan D. Perón 4190, 1181 Buenos Aires, Argentina.
authors.forename: Carina
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Puntel
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors.forename: Mariano
authors.initials: M
authors.lastname: Salibe
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
authors.forename: Ariel
authors.initials: A
authors.lastname: Chernomoretz
authors.affiliation: Leloir Institute Foundation, Institute for Biochemical Research of Buenos Aires - IIBBA CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina. Electronic address: fpitossi@leloir.org.ar.
authors.forename: Fernando Juan
authors.initials: FJ
authors.lastname: Pitossi
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D016023:Integrins; D053773:Transforming Growth Factor beta1; C084612:fibulin 2
keywords: Adult neural stem cells; Adult neurogenesis; Fibulin-2; Genomics; Subventricular zone; Transforming growth factor-beta 1