Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia
Activated microglia act as a double-edged sword for stroke. In the acute phase of stroke, activated microglia might deteriorate neurological function. Therefore, it is of great clinical transforming potential to explore drugs or methods that can inhibit abnormal activation of microglia in the acute...
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MDPI AG
2023-01-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/2/268 |
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| author | Hongyan Liao Jiagui Huang Jie Liu Yue Chen Huimin Zhu Xuemei Li Jun Wen Qin Xiang Qin Yang |
| author_facet | Hongyan Liao Jiagui Huang Jie Liu Yue Chen Huimin Zhu Xuemei Li Jun Wen Qin Xiang Qin Yang |
| author_sort | Hongyan Liao |
| collection | DOAJ |
| description | Activated microglia act as a double-edged sword for stroke. In the acute phase of stroke, activated microglia might deteriorate neurological function. Therefore, it is of great clinical transforming potential to explore drugs or methods that can inhibit abnormal activation of microglia in the acute phase of stroke to improve neurological function after stroke. Resveratrol has a potential effect of regulating microglial activation and anti-inflammation. However, the molecular mechanism of resveratrol-inhibiting microglial activation has not been fully clarified. Smoothened (Smo) belongs to the Hedgehog (Hh) signaling pathway. Smo activation is the critical step that transmits the Hh signal across the primary cilia to the cytoplasm. Moreover, activated Smo can improve neurological function via regulating oxidative stress, inflammation, apoptosis, neurogenesis, oligodendrogenesis, axonal remodeling, and so on. More studies have indicated that resveratrol can activate Smo. However, it is currently unknown whether resveratrol inhibits microglial activation via Smo. Therefore, in this study, N9 microglia in vitro and mice in vivo were used to investigate whether resveratrol inhibited microglial activation after oxygen-glucose deprivation/reoxygenation (OGD/R) or middle cerebral artery occlusion/reperfusion (MCAO/R) injury and improved functional outcome via triggering translocation of Smo in primary cilia. We definitively found that microglia had primary cilia; resveratrol partially inhibited activation and inflammation of microglia, improved functional outcome after OGD/R and MCAO/R injury, and triggered translocation of Smo to primary cilia. On the contrary, Smo antagonist cyclopamine canceled the above effects of resveratrol. The study suggested that Smo receptor might be a therapeutic target of resveratrol for contributing to inhibit microglial activation in the acute phase of stroke. |
| first_indexed | 2024-03-11T08:35:06Z |
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| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T08:35:06Z |
| publishDate | 2023-01-01 |
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| series | Journal of Personalized Medicine |
| spelling | doaj.art-deeab34c8c604e8bbeaa3c71c7ea9c102023-11-16T21:33:03ZengMDPI AGJournal of Personalized Medicine2075-44262023-01-0113226810.3390/jpm13020268Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary CiliaHongyan Liao0Jiagui Huang1Jie Liu2Yue Chen3Huimin Zhu4Xuemei Li5Jun Wen6Qin Xiang7Qin Yang8Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Longevity District People’s Hospital of Chongqing, Chongqing 401220, ChinaDepartment of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaActivated microglia act as a double-edged sword for stroke. In the acute phase of stroke, activated microglia might deteriorate neurological function. Therefore, it is of great clinical transforming potential to explore drugs or methods that can inhibit abnormal activation of microglia in the acute phase of stroke to improve neurological function after stroke. Resveratrol has a potential effect of regulating microglial activation and anti-inflammation. However, the molecular mechanism of resveratrol-inhibiting microglial activation has not been fully clarified. Smoothened (Smo) belongs to the Hedgehog (Hh) signaling pathway. Smo activation is the critical step that transmits the Hh signal across the primary cilia to the cytoplasm. Moreover, activated Smo can improve neurological function via regulating oxidative stress, inflammation, apoptosis, neurogenesis, oligodendrogenesis, axonal remodeling, and so on. More studies have indicated that resveratrol can activate Smo. However, it is currently unknown whether resveratrol inhibits microglial activation via Smo. Therefore, in this study, N9 microglia in vitro and mice in vivo were used to investigate whether resveratrol inhibited microglial activation after oxygen-glucose deprivation/reoxygenation (OGD/R) or middle cerebral artery occlusion/reperfusion (MCAO/R) injury and improved functional outcome via triggering translocation of Smo in primary cilia. We definitively found that microglia had primary cilia; resveratrol partially inhibited activation and inflammation of microglia, improved functional outcome after OGD/R and MCAO/R injury, and triggered translocation of Smo to primary cilia. On the contrary, Smo antagonist cyclopamine canceled the above effects of resveratrol. The study suggested that Smo receptor might be a therapeutic target of resveratrol for contributing to inhibit microglial activation in the acute phase of stroke.https://www.mdpi.com/2075-4426/13/2/268resveratrolmicroglial activationprimary ciliasonic hedgehog signalingstroke |
| spellingShingle | Hongyan Liao Jiagui Huang Jie Liu Yue Chen Huimin Zhu Xuemei Li Jun Wen Qin Xiang Qin Yang Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia Journal of Personalized Medicine resveratrol microglial activation primary cilia sonic hedgehog signaling stroke |
| title | Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia |
| title_full | Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia |
| title_fullStr | Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia |
| title_full_unstemmed | Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia |
| title_short | Resveratrol Inhibits Activation of Microglia after Stroke through Triggering Translocation of Smo to Primary Cilia |
| title_sort | resveratrol inhibits activation of microglia after stroke through triggering translocation of smo to primary cilia |
| topic | resveratrol microglial activation primary cilia sonic hedgehog signaling stroke |
| url | https://www.mdpi.com/2075-4426/13/2/268 |
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