Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN)
Microglia activation contributes to Alzheimer’s disease (AD) etiology, and microglia migration is a fundamental function during microglia activation. The repressor element-1 silencing transcription factor (REST), a powerful transcriptional factor, was found to play a neuroprotective role in AD. Desp...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2020/8855822 |
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| author | Tongya Yu Yingying Lin Yuzhen Xu Yunxiao Dou Feihong Wang Hui Quan Yanxin Zhao Xueyuan Liu |
| author_facet | Tongya Yu Yingying Lin Yuzhen Xu Yunxiao Dou Feihong Wang Hui Quan Yanxin Zhao Xueyuan Liu |
| author_sort | Tongya Yu |
| collection | DOAJ |
| description | Microglia activation contributes to Alzheimer’s disease (AD) etiology, and microglia migration is a fundamental function during microglia activation. The repressor element-1 silencing transcription factor (REST), a powerful transcriptional factor, was found to play a neuroprotective role in AD. Despite its possible role in disease progression, little is known about whether REST participates in microglia migration. In this study, we aimed to explore the function of REST and its molecular basis during microglia migration under Aβ1-42-treated pathological conditions. When treated by Aβ1-42 REST was upregulated through JAK2/STAT3 signal pathway in BV2 cells. And transwell coculture system was used to evaluate cell migration function of microglia-like BV2. Small interfering RNA (siRNA) targeting progranulin (PGRN) were delivered into BV2 cells, and results showed that PGRN functions to promote BV2 migration. REST expression was inhibited by sh-RNA, which induced BV2 cell migration obviously. On the contrary, REST was overexpressed by REST recombinant plasmid transfection, which repressed BV2 cell migration, indicating that REST may act as a repressor of cell migration. To more comprehensively examine the molecular basis, we analyzed the promoter sequence of PGRN and found that it has the potential binding site of REST. Moreover, knocking-down of REST can increase the expression of PGRN, which confirms the inhibiting effect of REST on PGRN expression. Further detection of double luciferase reporter gene also confirmed the inhibition of REST on the activity of PGRN promoter, indicating that REST may be an inhibitory transcription factor of PGRN which governs microglia-like BV2 cell migration. In conclusion, the present study demonstrates that transcription factor REST may act as a repressor of microglia migration through PGRN. |
| format | Article |
| id | doaj-art-4cebebfa453a43c7a950972fd649e579 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-4cebebfa453a43c7a950972fd649e5792025-02-03T01:04:27ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/88558228855822Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN)Tongya Yu0Yingying Lin1Yuzhen Xu2Yunxiao Dou3Feihong Wang4Hui Quan5Yanxin Zhao6Xueyuan Liu7Shanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaShanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaShanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaShanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaShanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaShanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaShanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaShanghai Tenth People’s Hospital of Tongji University, Tongji University, Middle Yanchang Rd. 301#, Jingan District, Shanghai, 200072, ChinaMicroglia activation contributes to Alzheimer’s disease (AD) etiology, and microglia migration is a fundamental function during microglia activation. The repressor element-1 silencing transcription factor (REST), a powerful transcriptional factor, was found to play a neuroprotective role in AD. Despite its possible role in disease progression, little is known about whether REST participates in microglia migration. In this study, we aimed to explore the function of REST and its molecular basis during microglia migration under Aβ1-42-treated pathological conditions. When treated by Aβ1-42 REST was upregulated through JAK2/STAT3 signal pathway in BV2 cells. And transwell coculture system was used to evaluate cell migration function of microglia-like BV2. Small interfering RNA (siRNA) targeting progranulin (PGRN) were delivered into BV2 cells, and results showed that PGRN functions to promote BV2 migration. REST expression was inhibited by sh-RNA, which induced BV2 cell migration obviously. On the contrary, REST was overexpressed by REST recombinant plasmid transfection, which repressed BV2 cell migration, indicating that REST may act as a repressor of cell migration. To more comprehensively examine the molecular basis, we analyzed the promoter sequence of PGRN and found that it has the potential binding site of REST. Moreover, knocking-down of REST can increase the expression of PGRN, which confirms the inhibiting effect of REST on PGRN expression. Further detection of double luciferase reporter gene also confirmed the inhibition of REST on the activity of PGRN promoter, indicating that REST may be an inhibitory transcription factor of PGRN which governs microglia-like BV2 cell migration. In conclusion, the present study demonstrates that transcription factor REST may act as a repressor of microglia migration through PGRN.http://dx.doi.org/10.1155/2020/8855822 |
| spellingShingle | Tongya Yu Yingying Lin Yuzhen Xu Yunxiao Dou Feihong Wang Hui Quan Yanxin Zhao Xueyuan Liu Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN) Neural Plasticity |
| title | Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN) |
| title_full | Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN) |
| title_fullStr | Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN) |
| title_full_unstemmed | Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN) |
| title_short | Repressor Element 1 Silencing Transcription Factor (REST) Governs Microglia-Like BV2 Cell Migration via Progranulin (PGRN) |
| title_sort | repressor element 1 silencing transcription factor rest governs microglia like bv2 cell migration via progranulin pgrn |
| url | http://dx.doi.org/10.1155/2020/8855822 |
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