Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5
Joint Authors
Ning, You
Kalionis, Bill
Huang, Jianhua
Bian, Qin
Dong, Jingcheng
Shen, Ziyin
Wu, Junzhen
Xia, Shi-Jin
Tai, Xiantao
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-07-09
Country of Publication
Egypt
No. of Pages
12
Abstract EN
Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions and/or in response to tissue damage.
NSCs open a new way of treatment of the injured central nervous system and neurodegenerative disorders.
Thus far, few drugs have been developed for controlling NSC functions.
Here, the effect as well as mechanism of oleanolic acid (OA), a pentacyclic triterpenoid, on NSC function was investigated.
We found OA significantly inhibited neurosphere formation in a dose-dependent manner and achieved a maximum effect at 10 nM.
OA also reduced 5-ethynyl-2′-deoxyuridine (EdU) incorporation into NSCs, which was indicative of inhibited NSC proliferation.
Western blotting analysis revealed the protein levels of neuron-specific marker tubulin-βIII (TuJ1) and Mash1 were increased whilst the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased.
Immunofluorescence analysis showed OA significantly elevated the percentage of TuJ1-positive cells and reduced GFAP-positive cells.
Using DNA microarray analysis, 183 genes were differentially regulated by OA.
Through transcription factor binding site analyses of the upstream regulatory sequences of these genes, 87 genes were predicted to share a common motif for Nkx-2.5 binding.
Finally, small interfering RNA (siRNA) methodology was used to silence Nkx-2.5 expression and found silence of Nkx-2.5 alone did not change the expression of TuJ-1 and the percentage of TuJ-1-positive cells.
But in combination of OA treatment and silence of Nkx-2.5, most effects of OA on NSCs were abolished.
These results indicated that OA is an effective inducer for NSCs differentiation into neurons at least partially by Nkx-2.5-dependent mechanism.
American Psychological Association (APA)
Ning, You& Huang, Jianhua& Kalionis, Bill& Bian, Qin& Dong, Jingcheng& Wu, Junzhen…[et al.]. 2015. Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5. Stem Cells International،Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1076327
Modern Language Association (MLA)
Ning, You…[et al.]. Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5. Stem Cells International No. 2015 (2015), pp.1-12.
https://search.emarefa.net/detail/BIM-1076327
American Medical Association (AMA)
Ning, You& Huang, Jianhua& Kalionis, Bill& Bian, Qin& Dong, Jingcheng& Wu, Junzhen…[et al.]. Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5. Stem Cells International. 2015. Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1076327
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1076327