Fibulin-2 is a key mediator of the pro-neurogenic effect of TGF-beta1 on adult neural stem cells

RADICE P.; MATHIEU P.; LEAL MC.; FARIAS MI.; FERRARI; PUNTEL M.; SALIBE M.; CHERNOMORETZ A.; PITOSSI

MOLECULAR AND CELLULAR NEUROSCIENCES.

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2015 vol. 67 p. 65 - 73

1044-7431

Transforming growth factor beta 1 (TGF-beta1), an anti-inflammatory cytokine, has been shown to have proneurogeniceffects on adult Neural Stem Cells (aNSC) from the dentate gyrus and in vivo models. Here, we expandedthe 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 tomediate its effect. 10 candidategeneswere identified by microarray analysis and further validated by qRT-PCR. Of these, Fibulin-2was increased477-fold and its inhibition by siRNA blocks TGF-beta1 pro-neurogenic effect. Curiously, Fibulin-2was notexpressed by aNSC but by a GFAP-positive population in the culture, suggesting an indirect mechanismof action.TGF-beta1 also induced Fibulin-2 in the SVZ in vivo. Interestingly, 5 out of the 10 candidate genes identified areknown 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 integrinsand provided proof that Fibulin-2 is a major mediator of the pro-neurogenic effects of TGF-beta1. These datashould contribute to further exploring the molecular mechanism of adult neurogenesis of the genes identifiedand the involvement of the integrin pathway on adult neurogenesis.