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Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts
Most recent studies reported that FoxO1 transcription factor was a negative regulator of myogenesis under serum withdrawal condition, a situation not actually found in vivo. Therefore, the role of FoxO1 in myogenesis should be re-examined under more physiologically relevant conditions. Here we found...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923792/ https://www.ncbi.nlm.nih.gov/pubmed/24551104 http://dx.doi.org/10.1371/journal.pone.0088450 |
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author | Wu, Yi Ju Fang, Yen Hsin Chi, Hsiang Cheng Chang, Li Chiung Chung, Shih Ying Huang, Wei Chieh Wang, Xiao Wen Lee, Kuan Wei Chen, Shen Liang |
author_facet | Wu, Yi Ju Fang, Yen Hsin Chi, Hsiang Cheng Chang, Li Chiung Chung, Shih Ying Huang, Wei Chieh Wang, Xiao Wen Lee, Kuan Wei Chen, Shen Liang |
author_sort | Wu, Yi Ju |
collection | PubMed |
description | Most recent studies reported that FoxO1 transcription factor was a negative regulator of myogenesis under serum withdrawal condition, a situation not actually found in vivo. Therefore, the role of FoxO1 in myogenesis should be re-examined under more physiologically relevant conditions. Here we found that FoxO1 was preferentially localized to nucleus in proliferating (PMB) and confluent myoblasts (CMB) and its nuclear exclusion was a prerequisite for formation of multinucleated myotubes (MT). The nuclear shuttling of FoxO1 in PMB could be prevented by leptomycin B and we further found that cytoplasmic accumulation of FoxO1 in myotubes was caused by the blockade of its nuclear import. Although over-expression of wildtype FoxO1 in C2C12 myoblasts significantly blocked their myogenic differentiation under serum withdrawal condition, application of insulin and LiCl, an activator of Wnt signaling pathway, to these cells successfully rescued their myogenic differentiation and generated myotubes with larger diameters. Interestingly, insulin treatment significantly reduced FoxO1 level and also delayed nuclear re-accumulation of FoxO1 triggered by mitogen deprivation. We further found that FoxO1 directly repressed the promoter activity of myogenic genes and this repression can be relieved by insulin and LiCl treatment. These results suggest that FoxO1 inhibits myogenesis in serum withdrawal condition but turns into a hypertrophy potentiator when other myogenic signals, such as Wnt and insulin, are available. |
format | Online Article Text |
id | pubmed-3923792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39237922014-02-18 Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts Wu, Yi Ju Fang, Yen Hsin Chi, Hsiang Cheng Chang, Li Chiung Chung, Shih Ying Huang, Wei Chieh Wang, Xiao Wen Lee, Kuan Wei Chen, Shen Liang PLoS One Research Article Most recent studies reported that FoxO1 transcription factor was a negative regulator of myogenesis under serum withdrawal condition, a situation not actually found in vivo. Therefore, the role of FoxO1 in myogenesis should be re-examined under more physiologically relevant conditions. Here we found that FoxO1 was preferentially localized to nucleus in proliferating (PMB) and confluent myoblasts (CMB) and its nuclear exclusion was a prerequisite for formation of multinucleated myotubes (MT). The nuclear shuttling of FoxO1 in PMB could be prevented by leptomycin B and we further found that cytoplasmic accumulation of FoxO1 in myotubes was caused by the blockade of its nuclear import. Although over-expression of wildtype FoxO1 in C2C12 myoblasts significantly blocked their myogenic differentiation under serum withdrawal condition, application of insulin and LiCl, an activator of Wnt signaling pathway, to these cells successfully rescued their myogenic differentiation and generated myotubes with larger diameters. Interestingly, insulin treatment significantly reduced FoxO1 level and also delayed nuclear re-accumulation of FoxO1 triggered by mitogen deprivation. We further found that FoxO1 directly repressed the promoter activity of myogenic genes and this repression can be relieved by insulin and LiCl treatment. These results suggest that FoxO1 inhibits myogenesis in serum withdrawal condition but turns into a hypertrophy potentiator when other myogenic signals, such as Wnt and insulin, are available. Public Library of Science 2014-02-13 /pmc/articles/PMC3923792/ /pubmed/24551104 http://dx.doi.org/10.1371/journal.pone.0088450 Text en © 2014 Wu 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wu, Yi Ju Fang, Yen Hsin Chi, Hsiang Cheng Chang, Li Chiung Chung, Shih Ying Huang, Wei Chieh Wang, Xiao Wen Lee, Kuan Wei Chen, Shen Liang Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts |
title | Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts |
title_full | Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts |
title_fullStr | Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts |
title_full_unstemmed | Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts |
title_short | Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts |
title_sort | insulin and licl synergistically rescue myogenic differentiation of foxo1 over-expressed myoblasts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923792/ https://www.ncbi.nlm.nih.gov/pubmed/24551104 http://dx.doi.org/10.1371/journal.pone.0088450 |
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