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Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e
Defective brain hormonal signaling and autophagy have been associated with neurodegeneration after brain insults, characterized by neuronal loss and cognitive dysfunction. However, few studies have linked them in the context of brain injury. Insulin-like growth factor-1 (IGF-1) is an important hormo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433209/ https://www.ncbi.nlm.nih.gov/pubmed/36062186 http://dx.doi.org/10.1155/2022/3504279 |
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author | Dabin, Ren Wei, Chen Liang, Shu Ke, Cao Zhihan, Wang Ping, Zheng |
author_facet | Dabin, Ren Wei, Chen Liang, Shu Ke, Cao Zhihan, Wang Ping, Zheng |
author_sort | Dabin, Ren |
collection | PubMed |
description | Defective brain hormonal signaling and autophagy have been associated with neurodegeneration after brain insults, characterized by neuronal loss and cognitive dysfunction. However, few studies have linked them in the context of brain injury. Insulin-like growth factor-1 (IGF-1) is an important hormone that contributes to growth, cell proliferation, and autophagy and is also expressed in the brain. Here, we assessed the clinical data from TBI patients and performed both in vitro and in vivo experiments with proteomic and gene-chip analysis to assess the functions of IGF-1 in mitophagy following TBI. We show that reduced plasma IGF-1 is correlated with cognition in TBI patients. Overexpression of astrocytic IGF-1 improves cognitive dysfunction and mitophagy in TBI mice. Mechanically, proteomics data show that the IGF-1-related NF-κB pathway transcriptionally regulates decapping mRNA2 (Dcp2) and miR-let-7, together with IGF-1R to orchestrate mitophagy in TBI. Finally, we demonstrate that brain injury induces impaired mitophagy at the chronic stage and that IGF-1 treatment could facilitate the mitophagy markers via exosomal miR-let-7e. By showing that IGF-1 is an important mediator of the beneficial effect of the neural-endocrine network in TBI models, our findings place IGF-1/IGF-1R as a potential target capable of noncoding RNAs and opposing mitophagy failure and cognitive impairment in TBI. |
format | Online Article Text |
id | pubmed-9433209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-94332092022-09-01 Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e Dabin, Ren Wei, Chen Liang, Shu Ke, Cao Zhihan, Wang Ping, Zheng Oxid Med Cell Longev Research Article Defective brain hormonal signaling and autophagy have been associated with neurodegeneration after brain insults, characterized by neuronal loss and cognitive dysfunction. However, few studies have linked them in the context of brain injury. Insulin-like growth factor-1 (IGF-1) is an important hormone that contributes to growth, cell proliferation, and autophagy and is also expressed in the brain. Here, we assessed the clinical data from TBI patients and performed both in vitro and in vivo experiments with proteomic and gene-chip analysis to assess the functions of IGF-1 in mitophagy following TBI. We show that reduced plasma IGF-1 is correlated with cognition in TBI patients. Overexpression of astrocytic IGF-1 improves cognitive dysfunction and mitophagy in TBI mice. Mechanically, proteomics data show that the IGF-1-related NF-κB pathway transcriptionally regulates decapping mRNA2 (Dcp2) and miR-let-7, together with IGF-1R to orchestrate mitophagy in TBI. Finally, we demonstrate that brain injury induces impaired mitophagy at the chronic stage and that IGF-1 treatment could facilitate the mitophagy markers via exosomal miR-let-7e. By showing that IGF-1 is an important mediator of the beneficial effect of the neural-endocrine network in TBI models, our findings place IGF-1/IGF-1R as a potential target capable of noncoding RNAs and opposing mitophagy failure and cognitive impairment in TBI. Hindawi 2022-08-24 /pmc/articles/PMC9433209/ /pubmed/36062186 http://dx.doi.org/10.1155/2022/3504279 Text en Copyright © 2022 Ren Dabin et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Dabin, Ren Wei, Chen Liang, Shu Ke, Cao Zhihan, Wang Ping, Zheng Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e |
title | Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e |
title_full | Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e |
title_fullStr | Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e |
title_full_unstemmed | Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e |
title_short | Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e |
title_sort | astrocytic igf-1 and igf-1r orchestrate mitophagy in traumatic brain injury via exosomal mir-let-7e |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433209/ https://www.ncbi.nlm.nih.gov/pubmed/36062186 http://dx.doi.org/10.1155/2022/3504279 |
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