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Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice

Ependymal cells have been suggested to act as neural stem cells and exert beneficial effects after spinal cord injury (SCI). However, the molecular mechanism underlying ependymal cell regulation after SCI remains unknown. To examine the possible effect of IL-17A on ependymal cell proliferation after...

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Autores principales: Miyajima, Hisao, Itokazu, Takahide, Tanabe, Shogo, Yamashita, Toshihide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333070/
https://www.ncbi.nlm.nih.gov/pubmed/34344859
http://dx.doi.org/10.1038/s41419-021-04064-1
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author Miyajima, Hisao
Itokazu, Takahide
Tanabe, Shogo
Yamashita, Toshihide
author_facet Miyajima, Hisao
Itokazu, Takahide
Tanabe, Shogo
Yamashita, Toshihide
author_sort Miyajima, Hisao
collection PubMed
description Ependymal cells have been suggested to act as neural stem cells and exert beneficial effects after spinal cord injury (SCI). However, the molecular mechanism underlying ependymal cell regulation after SCI remains unknown. To examine the possible effect of IL-17A on ependymal cell proliferation after SCI, we locally administrated IL-17A neutralizing antibody to the injured spinal cord of a contusion SCI mouse model, and revealed that IL-17A neutralization promoted ependymal cell proliferation, which was paralleled by functional recovery and axonal reorganization of both the corticospinal tract and the raphespinal tract. Further, to test whether ependymal cell-specific manipulation of IL-17A signaling is enough to affect the outcomes of SCI, we generated ependymal cell-specific conditional IL-17RA-knockout mice and analyzed their anatomical and functional response to SCI. As a result, conditional knockout of IL-17RA in ependymal cells enhanced both axonal growth and functional recovery, accompanied by an increase in mRNA expression of neurotrophic factors. Thus, Ependymal cells may enhance the regenerative process partially by secreting neurotrophic factors, and IL-17A stimulation negatively regulates this beneficial effect. Molecular manipulation of ependymal cells might be a viable strategy for improving functional recovery.
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spelling pubmed-83330702021-08-05 Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice Miyajima, Hisao Itokazu, Takahide Tanabe, Shogo Yamashita, Toshihide Cell Death Dis Article Ependymal cells have been suggested to act as neural stem cells and exert beneficial effects after spinal cord injury (SCI). However, the molecular mechanism underlying ependymal cell regulation after SCI remains unknown. To examine the possible effect of IL-17A on ependymal cell proliferation after SCI, we locally administrated IL-17A neutralizing antibody to the injured spinal cord of a contusion SCI mouse model, and revealed that IL-17A neutralization promoted ependymal cell proliferation, which was paralleled by functional recovery and axonal reorganization of both the corticospinal tract and the raphespinal tract. Further, to test whether ependymal cell-specific manipulation of IL-17A signaling is enough to affect the outcomes of SCI, we generated ependymal cell-specific conditional IL-17RA-knockout mice and analyzed their anatomical and functional response to SCI. As a result, conditional knockout of IL-17RA in ependymal cells enhanced both axonal growth and functional recovery, accompanied by an increase in mRNA expression of neurotrophic factors. Thus, Ependymal cells may enhance the regenerative process partially by secreting neurotrophic factors, and IL-17A stimulation negatively regulates this beneficial effect. Molecular manipulation of ependymal cells might be a viable strategy for improving functional recovery. Nature Publishing Group UK 2021-08-03 /pmc/articles/PMC8333070/ /pubmed/34344859 http://dx.doi.org/10.1038/s41419-021-04064-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Miyajima, Hisao
Itokazu, Takahide
Tanabe, Shogo
Yamashita, Toshihide
Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice
title Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice
title_full Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice
title_fullStr Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice
title_full_unstemmed Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice
title_short Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice
title_sort interleukin-17a regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333070/
https://www.ncbi.nlm.nih.gov/pubmed/34344859
http://dx.doi.org/10.1038/s41419-021-04064-1
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