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

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...

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Veröffentlicht in:Biochemical and biophysical research communications 2015-08, Vol.464 (2), p.596-602
Hauptverfasser: Retamales, A., Zuloaga, R., Valenzuela, C.A., Gallardo-Escarate, C., Molina, A., Valdés, J.A.
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container_issue 2
container_start_page 596
container_title Biochemical and biophysical research communications
container_volume 464
creator Retamales, A.
Zuloaga, R.
Valenzuela, C.A.
Gallardo-Escarate, C.
Molina, A.
Valdés, J.A.
description 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. •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_str_mv 10.1016/j.bbrc.2015.07.018
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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. 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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. •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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26151859</pmid><doi>10.1016/j.bbrc.2015.07.018</doi><tpages>7</tpages></addata></record>
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ispartof Biochemical and biophysical research communications, 2015-08, Vol.464 (2), p.596-602
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language eng
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source MEDLINE; Elsevier ScienceDirect Journals
subjects 60 APPLIED LIFE SCIENCES
Animals
Cell Differentiation - physiology
Crosstalk
FIBERS
GENES
GROWTH FACTORS
IGF-1
INSULIN
Insulin-Like Growth Factor I - physiology
INTERACTIONS
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Myoblast differentiation
MYOBLASTS
Myoblasts - cytology
Myostatin
Myostatin - metabolism
PLANT GROWTH
Rats
RECEPTORS
Signal Transduction - physiology
SIGNALS
Smad3 Protein - metabolism
STIMULATION
TRANSCRIPTION
TRANSCRIPTION FACTORS
VERTEBRATES
title Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation
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