Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos
The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributors to the failure of sensory and motor functional recovery following spinal cord injury. Heat shock transcription factor 1 (HSF1), a master regulator of the heat shock response, plays neurogeneti...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=9;spage=2011;epage=2018;aulast=He |
| _version_ | 1797866439450820608 |
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| author | Bing-Qiang He Ai-Cheng Li Yu-Xuan Hou Hui Li Xing-Yuan Zhang Hui-Fei Hao Hong-Hua Song Ri-Xin Cai Ying-Jie Wang Yue Zhou Yong-Jun Wang |
| author_facet | Bing-Qiang He Ai-Cheng Li Yu-Xuan Hou Hui Li Xing-Yuan Zhang Hui-Fei Hao Hong-Hua Song Ri-Xin Cai Ying-Jie Wang Yue Zhou Yong-Jun Wang |
| author_sort | Bing-Qiang He |
| collection | DOAJ |
| description | The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributors to the failure of sensory and motor functional recovery following spinal cord injury. Heat shock transcription factor 1 (HSF1), a master regulator of the heat shock response, plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system. However, the underlying mechanism has not been fully elucidated. In the present study, we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1 (gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury. gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation. gHSF1 overexpression in gecko primary neurons significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3, and facilitated neuronal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways. Furthermore, gHSF1 efficiently inhibited the macrophage-mediated inflammatory response by inactivating IkappaB-alpha/NF-kappaB signaling. Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation, and provide new avenues of investigation for promoting spinal cord injury repair in mammals. |
| first_indexed | 2024-04-09T23:24:11Z |
| format | Article |
| id | doaj.art-7443bc5045c84e058fa2e16c498a20b0 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-09T23:24:11Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-7443bc5045c84e058fa2e16c498a20b02023-03-21T11:23:56ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-011892011201810.4103/1673-5374.366495Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckosBing-Qiang HeAi-Cheng LiYu-Xuan HouHui LiXing-Yuan ZhangHui-Fei HaoHong-Hua SongRi-Xin CaiYing-Jie WangYue ZhouYong-Jun WangThe low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributors to the failure of sensory and motor functional recovery following spinal cord injury. Heat shock transcription factor 1 (HSF1), a master regulator of the heat shock response, plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system. However, the underlying mechanism has not been fully elucidated. In the present study, we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1 (gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury. gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation. gHSF1 overexpression in gecko primary neurons significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3, and facilitated neuronal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways. Furthermore, gHSF1 efficiently inhibited the macrophage-mediated inflammatory response by inactivating IkappaB-alpha/NF-kappaB signaling. Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation, and provide new avenues of investigation for promoting spinal cord injury repair in mammals.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=9;spage=2011;epage=2018;aulast=Heapoptosis; gecko; heat shock factor 1; inflammation; neuron; regeneration; spinal cord; suppressor of cytokine signaling-3 |
| spellingShingle | Bing-Qiang He Ai-Cheng Li Yu-Xuan Hou Hui Li Xing-Yuan Zhang Hui-Fei Hao Hong-Hua Song Ri-Xin Cai Ying-Jie Wang Yue Zhou Yong-Jun Wang Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos Neural Regeneration Research apoptosis; gecko; heat shock factor 1; inflammation; neuron; regeneration; spinal cord; suppressor of cytokine signaling-3 |
| title | Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos |
| title_full | Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos |
| title_fullStr | Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos |
| title_full_unstemmed | Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos |
| title_short | Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos |
| title_sort | heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos |
| topic | apoptosis; gecko; heat shock factor 1; inflammation; neuron; regeneration; spinal cord; suppressor of cytokine signaling-3 |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=9;spage=2011;epage=2018;aulast=He |
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