Fibulin-2 is a key mediator of the pro-neurogenic effect of TGF-beta1 on adult neural stem cells
Open accessAbstract
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.
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Fibulin-2 mediates TGF-beta1 effects on adult neural stem cells.
“Interestingly, fibulin-1 mutations are associated with cognitive deficits in the human and fibulin-2 mediates TGF-beta1 effects on adult neural stem cells50,51.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [51]
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References 37 · Cited by 25
- Authors
- Radice, P. D., Mathieu, P., Leal, M. C., Farías, M. I., Ferrari, C., Puntel, M., Salibe, M., Chernomoretz, A., & Pitossi, F. J.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Hospital Italiano de Buenos Aires (AR)
- Corresponding author
- Pitossi, Fernando Juan
- ORCID
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 67
- Pages
- 75-83
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W617921437
- Cited by
- 25
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-nd)
- Funders
- ANPCyT
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- fibulin-2, TGF-β1, adult neural stem cells, subventricular zone, adult neurogenesis, integrins, candidate gene identification, siRNA knockdown
- MeSH terms
- Animals, Astrocytes, Calcium-Binding Proteins, Cells, Cultured, Integrins, Extracellular Matrix Proteins, Rats, Wistar, Lateral Ventricles, Rats, Adult Stem Cells, Transforming Growth Factor beta1, Neurogenesis, Neural Stem Cells
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