Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5
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...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2015/672312 |
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| author | You Ning Jianhua Huang Bill Kalionis Qin Bian Jingcheng Dong Junzhen Wu Xiantao Tai Shijin Xia Ziyin Shen |
| author_facet | You Ning Jianhua Huang Bill Kalionis Qin Bian Jingcheng Dong Junzhen Wu Xiantao Tai Shijin Xia Ziyin Shen |
| author_sort | You Ning |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2bebb0328fce459c9e5ff9402c6a119d |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-2bebb0328fce459c9e5ff9402c6a119d2025-02-03T01:00:53ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/672312672312Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5You Ning0Jianhua Huang1Bill Kalionis2Qin Bian3Jingcheng Dong4Junzhen Wu5Xiantao Tai6Shijin Xia7Ziyin Shen8Institute of Integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, ChinaInstitute of Integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Obstetrics and Gynaecology and Department of Perinatal Medicine Pregnancy Research Centre, Royal Women’s Hospital, University of Melbourne, Parkville, VIC 3052, AustraliaInstitute of Integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, ChinaInstitute of Integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, ChinaShanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai 200040, ChinaSchool of Acupuncture, Massage and Rehabilitation, Yunnan University of Traditional Chinese Medicine, Kunming 650500, ChinaShanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai 200040, ChinaInstitute of Integrated Traditional Chinese Medicine and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, ChinaNeural 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.http://dx.doi.org/10.1155/2015/672312 |
| spellingShingle | You Ning Jianhua Huang Bill Kalionis Qin Bian Jingcheng Dong Junzhen Wu Xiantao Tai Shijin Xia Ziyin Shen Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5 Stem Cells International |
| title | Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5 |
| title_full | Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5 |
| title_fullStr | Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5 |
| title_full_unstemmed | Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5 |
| title_short | Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5 |
| title_sort | oleanolic acid induces differentiation of neural stem cells to neurons an involvement of transcription factor nkx 2 5 |
| url | http://dx.doi.org/10.1155/2015/672312 |
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