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GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway

Growth differentiation factor 11 (GDF11), belonging to the transforming factor-β superfamily, regulates anterior-posterior patterning and inhibits neurogenesis during embryonic development. However, recent studies recognized GDF11 as a rejuvenating (or anti-ageing) factor to reverse age-related card...

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Autores principales: Wang, Zongkui, Jiang, Peng, Liu, Fengjuan, Du, Xi, Ma, Li, Ye, Shengliang, Cao, Haijun, Sun, Pan, Su, Na, Lin, Fangzhao, Zhang, Rong, Li, Changqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602726/
https://www.ncbi.nlm.nih.gov/pubmed/36293138
http://dx.doi.org/10.3390/ijms232012279
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author Wang, Zongkui
Jiang, Peng
Liu, Fengjuan
Du, Xi
Ma, Li
Ye, Shengliang
Cao, Haijun
Sun, Pan
Su, Na
Lin, Fangzhao
Zhang, Rong
Li, Changqing
author_facet Wang, Zongkui
Jiang, Peng
Liu, Fengjuan
Du, Xi
Ma, Li
Ye, Shengliang
Cao, Haijun
Sun, Pan
Su, Na
Lin, Fangzhao
Zhang, Rong
Li, Changqing
author_sort Wang, Zongkui
collection PubMed
description Growth differentiation factor 11 (GDF11), belonging to the transforming factor-β superfamily, regulates anterior-posterior patterning and inhibits neurogenesis during embryonic development. However, recent studies recognized GDF11 as a rejuvenating (or anti-ageing) factor to reverse age-related cardiac hypertrophy, repair injured skeletal muscle, promote cognitive function, etc. The effects of GDF11 are contradictory and the mechanism of action is still not well clarified. The objective of the present study was to investigate effects of GDF11 on PC12 neural stem cells in vitro and to reveal the underlying mechanism. We systematically assessed the effects of GDF11 on the life activities of PC12 cells. GDF11 significantly suppressed cell proliferation and migration, promoted differentiation and apoptosis, and arrested cell cycle at G2/M phase. Both TMT-based proteomic analysis and phospho-antibody microarray revealed PI3K-Akt pathway was enriched when treated with GDF11. Inhibition of ALK5 or PI3K obviously attenuated the effects of GDF11 on PC12 neural stem cells, which exerted that GDF11 regulated neural stem cells through ALK5-dependent PI3K-Akt signaling pathway. In summary, these results demonstrated GDF11 could be a negative regulator for neurogenesis via ALK5 activating PI3K-Akt pathway when it directly acted on neural stem cells.
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spelling pubmed-96027262022-10-27 GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway Wang, Zongkui Jiang, Peng Liu, Fengjuan Du, Xi Ma, Li Ye, Shengliang Cao, Haijun Sun, Pan Su, Na Lin, Fangzhao Zhang, Rong Li, Changqing Int J Mol Sci Article Growth differentiation factor 11 (GDF11), belonging to the transforming factor-β superfamily, regulates anterior-posterior patterning and inhibits neurogenesis during embryonic development. However, recent studies recognized GDF11 as a rejuvenating (or anti-ageing) factor to reverse age-related cardiac hypertrophy, repair injured skeletal muscle, promote cognitive function, etc. The effects of GDF11 are contradictory and the mechanism of action is still not well clarified. The objective of the present study was to investigate effects of GDF11 on PC12 neural stem cells in vitro and to reveal the underlying mechanism. We systematically assessed the effects of GDF11 on the life activities of PC12 cells. GDF11 significantly suppressed cell proliferation and migration, promoted differentiation and apoptosis, and arrested cell cycle at G2/M phase. Both TMT-based proteomic analysis and phospho-antibody microarray revealed PI3K-Akt pathway was enriched when treated with GDF11. Inhibition of ALK5 or PI3K obviously attenuated the effects of GDF11 on PC12 neural stem cells, which exerted that GDF11 regulated neural stem cells through ALK5-dependent PI3K-Akt signaling pathway. In summary, these results demonstrated GDF11 could be a negative regulator for neurogenesis via ALK5 activating PI3K-Akt pathway when it directly acted on neural stem cells. MDPI 2022-10-14 /pmc/articles/PMC9602726/ /pubmed/36293138 http://dx.doi.org/10.3390/ijms232012279 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Zongkui
Jiang, Peng
Liu, Fengjuan
Du, Xi
Ma, Li
Ye, Shengliang
Cao, Haijun
Sun, Pan
Su, Na
Lin, Fangzhao
Zhang, Rong
Li, Changqing
GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway
title GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway
title_full GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway
title_fullStr GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway
title_full_unstemmed GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway
title_short GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway
title_sort gdf11 regulates pc12 neural stem cells via alk5-dependent pi3k-akt signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602726/
https://www.ncbi.nlm.nih.gov/pubmed/36293138
http://dx.doi.org/10.3390/ijms232012279
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