Cargando…

GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury

Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis...

Descripción completa

Detalles Bibliográficos
Autores principales: Weng, Jian, Wang, Yan-hua, Li, Ming, Zhang, Dian-ying, Jiang, Bao-guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879906/
https://www.ncbi.nlm.nih.gov/pubmed/29557384
http://dx.doi.org/10.4103/1673-5374.226403
_version_ 1783311078280658944
author Weng, Jian
Wang, Yan-hua
Li, Ming
Zhang, Dian-ying
Jiang, Bao-guo
author_facet Weng, Jian
Wang, Yan-hua
Li, Ming
Zhang, Dian-ying
Jiang, Bao-guo
author_sort Weng, Jian
collection PubMed
description Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migration and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of β-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta inhibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.
format Online
Article
Text
id pubmed-5879906
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Medknow Publications & Media Pvt Ltd
record_format MEDLINE/PubMed
spelling pubmed-58799062018-04-06 GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury Weng, Jian Wang, Yan-hua Li, Ming Zhang, Dian-ying Jiang, Bao-guo Neural Regen Res Research Article Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migration and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of β-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta inhibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury. Medknow Publications & Media Pvt Ltd 2018-02 /pmc/articles/PMC5879906/ /pubmed/29557384 http://dx.doi.org/10.4103/1673-5374.226403 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Research Article
Weng, Jian
Wang, Yan-hua
Li, Ming
Zhang, Dian-ying
Jiang, Bao-guo
GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury
title GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury
title_full GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury
title_fullStr GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury
title_full_unstemmed GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury
title_short GSK3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury
title_sort gsk3β inhibitor promotes myelination and mitigates muscle atrophy after peripheral nerve injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879906/
https://www.ncbi.nlm.nih.gov/pubmed/29557384
http://dx.doi.org/10.4103/1673-5374.226403
work_keys_str_mv AT wengjian gsk3binhibitorpromotesmyelinationandmitigatesmuscleatrophyafterperipheralnerveinjury
AT wangyanhua gsk3binhibitorpromotesmyelinationandmitigatesmuscleatrophyafterperipheralnerveinjury
AT liming gsk3binhibitorpromotesmyelinationandmitigatesmuscleatrophyafterperipheralnerveinjury
AT zhangdianying gsk3binhibitorpromotesmyelinationandmitigatesmuscleatrophyafterperipheralnerveinjury
AT jiangbaoguo gsk3binhibitorpromotesmyelinationandmitigatesmuscleatrophyafterperipheralnerveinjury