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Title: Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation

Abstract

Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletal myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on themore » complex crosstalk between both growth factors. - Highlights: • IGF-1 inhibits Myostatin canonical signaling pathway through IGF-1R/PI3K/Akt pathway. • IGF-1 promotes myoblast differentiation through a direct blocking of Myostatin signaling pathway. • IGF-1 induces the interaction of Akt with Smad3 in skeletal myoblast.« less

Authors:
; ;  [1];  [2];  [3];  [1];  [3];  [1];  [3]
  1. Laboratorio de Biotecnología Molecular, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago (Chile)
  2. Laboratory of Biotechnology and Aquatic Genomics, Universidad de Concepción, Concepción (Chile)
  3. (INCAR), P.O. Box 160-C, Concepción (Chile)
Publication Date:
OSTI Identifier:
22462213
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 464; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; FIBERS; GENES; GROWTH FACTORS; INSULIN; INTERACTIONS; MYOBLASTS; PLANT GROWTH; RECEPTORS; SIGNALS; STIMULATION; TRANSCRIPTION; TRANSCRIPTION FACTORS; VERTEBRATES

Citation Formats

Retamales, A., Zuloaga, R., Valenzuela, C.A., Gallardo-Escarate, C., Interdisciplinary Center for Aquaculture Research, Molina, A., Interdisciplinary Center for Aquaculture Research, Valdés, J.A., E-mail: jvaldes@unab.cl, and Interdisciplinary Center for Aquaculture Research. Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.07.018.
Retamales, A., Zuloaga, R., Valenzuela, C.A., Gallardo-Escarate, C., Interdisciplinary Center for Aquaculture Research, Molina, A., Interdisciplinary Center for Aquaculture Research, Valdés, J.A., E-mail: jvaldes@unab.cl, & Interdisciplinary Center for Aquaculture Research. Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation. United States. doi:10.1016/J.BBRC.2015.07.018.
Retamales, A., Zuloaga, R., Valenzuela, C.A., Gallardo-Escarate, C., Interdisciplinary Center for Aquaculture Research, Molina, A., Interdisciplinary Center for Aquaculture Research, Valdés, J.A., E-mail: jvaldes@unab.cl, and Interdisciplinary Center for Aquaculture Research. Fri . "Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation". United States. doi:10.1016/J.BBRC.2015.07.018.
@article{osti_22462213,
title = {Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation},
author = {Retamales, A. and Zuloaga, R. and Valenzuela, C.A. and Gallardo-Escarate, C. and Interdisciplinary Center for Aquaculture Research and Molina, A. and Interdisciplinary Center for Aquaculture Research and Valdés, J.A., E-mail: jvaldes@unab.cl and Interdisciplinary Center for Aquaculture Research},
abstractNote = {Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletal myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors. - Highlights: • IGF-1 inhibits Myostatin canonical signaling pathway through IGF-1R/PI3K/Akt pathway. • IGF-1 promotes myoblast differentiation through a direct blocking of Myostatin signaling pathway. • IGF-1 induces the interaction of Akt with Smad3 in skeletal myoblast.},
doi = {10.1016/J.BBRC.2015.07.018},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 464,
place = {United States},
year = {Fri Aug 21 00:00:00 EDT 2015},
month = {Fri Aug 21 00:00:00 EDT 2015}
}