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GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway

GDF11, a member of TGF-β superfamily, has recently received widespread attention as a novel anti-ageing/rejuvenation factor to reverse age-related dysfunctions in heart and skeletal muscle, and to induce angiogenesis and neurogenesis. However, these positive effects of GDF11 were challenged by sever...

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Autores principales: Wang, Zongkui, Dou, Miaomiao, Liu, Fengjuan, Jiang, Peng, Ye, Shengliang, Ma, Li, Cao, Haijun, Du, Xi, Sun, Pan, Su, Na, Lin, Fangzhao, Zhang, Rong, Li, Changqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128255/
https://www.ncbi.nlm.nih.gov/pubmed/30202652
http://dx.doi.org/10.7717/peerj.5524
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author Wang, Zongkui
Dou, Miaomiao
Liu, Fengjuan
Jiang, Peng
Ye, Shengliang
Ma, Li
Cao, Haijun
Du, Xi
Sun, Pan
Su, Na
Lin, Fangzhao
Zhang, Rong
Li, Changqing
author_facet Wang, Zongkui
Dou, Miaomiao
Liu, Fengjuan
Jiang, Peng
Ye, Shengliang
Ma, Li
Cao, Haijun
Du, Xi
Sun, Pan
Su, Na
Lin, Fangzhao
Zhang, Rong
Li, Changqing
author_sort Wang, Zongkui
collection PubMed
description GDF11, a member of TGF-β superfamily, has recently received widespread attention as a novel anti-ageing/rejuvenation factor to reverse age-related dysfunctions in heart and skeletal muscle, and to induce angiogenesis and neurogenesis. However, these positive effects of GDF11 were challenged by several other studies. Furthermore, the mechanism is still not well understood. In the present study, we evaluated the effects of GDF11 on C17.2 neural stem cells. GDF11 induced differentiation and apoptosis, and suppressed migration of C17.2 neural stem cells. In addition, GDF11 slightly increased cell viability after 24 h treatment, showed no effects on proliferation for about 10 days of cultivation, and slightly decreased cumulative population doubling for long-term treatment (p < 0.05). Phospho-proteome profiling array displayed that GDF11 significantly increased the phosphorylation of 13 serine/threonine kinases (p < 0.01), including p-p38, p-ERK and p-Akt, in C17.2 cells, which implied the activation of MAPK pathway. Western blot validated that the results of phospho-proteome profiling array were reliable. Based on functional analysis, we demonstrated that the differentially expressed proteins were mainly involved in signal transduction which was implicated in cellular behavior. Collectively, our findings suggest that, for neurogenesis, GDF11 might not be the desired rejuvenation factor, but a potential target for pharmacological blockade.
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spelling pubmed-61282552018-09-10 GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway Wang, Zongkui Dou, Miaomiao Liu, Fengjuan Jiang, Peng Ye, Shengliang Ma, Li Cao, Haijun Du, Xi Sun, Pan Su, Na Lin, Fangzhao Zhang, Rong Li, Changqing PeerJ Biochemistry GDF11, a member of TGF-β superfamily, has recently received widespread attention as a novel anti-ageing/rejuvenation factor to reverse age-related dysfunctions in heart and skeletal muscle, and to induce angiogenesis and neurogenesis. However, these positive effects of GDF11 were challenged by several other studies. Furthermore, the mechanism is still not well understood. In the present study, we evaluated the effects of GDF11 on C17.2 neural stem cells. GDF11 induced differentiation and apoptosis, and suppressed migration of C17.2 neural stem cells. In addition, GDF11 slightly increased cell viability after 24 h treatment, showed no effects on proliferation for about 10 days of cultivation, and slightly decreased cumulative population doubling for long-term treatment (p < 0.05). Phospho-proteome profiling array displayed that GDF11 significantly increased the phosphorylation of 13 serine/threonine kinases (p < 0.01), including p-p38, p-ERK and p-Akt, in C17.2 cells, which implied the activation of MAPK pathway. Western blot validated that the results of phospho-proteome profiling array were reliable. Based on functional analysis, we demonstrated that the differentially expressed proteins were mainly involved in signal transduction which was implicated in cellular behavior. Collectively, our findings suggest that, for neurogenesis, GDF11 might not be the desired rejuvenation factor, but a potential target for pharmacological blockade. PeerJ Inc. 2018-09-04 /pmc/articles/PMC6128255/ /pubmed/30202652 http://dx.doi.org/10.7717/peerj.5524 Text en ©2018 Wang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Wang, Zongkui
Dou, Miaomiao
Liu, Fengjuan
Jiang, Peng
Ye, Shengliang
Ma, Li
Cao, Haijun
Du, Xi
Sun, Pan
Su, Na
Lin, Fangzhao
Zhang, Rong
Li, Changqing
GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway
title GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway
title_full GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway
title_fullStr GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway
title_full_unstemmed GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway
title_short GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway
title_sort gdf11 induces differentiation and apoptosis and inhibits migration of c17.2 neural stem cells via modulating mapk signaling pathway
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128255/
https://www.ncbi.nlm.nih.gov/pubmed/30202652
http://dx.doi.org/10.7717/peerj.5524
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