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The cAMP response element binding protein (CREB) is activated by insulin-like growth factor-1 (IGF-1) and regulates

R Zuloaga1, E N Fuentes, A Molina

  • 1Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.

Biochemical and Biophysical Research Communications
|September 26, 2013
PubMed

Insights

Insulin-like Growth Factor 1 (IGF-1) activates the CREB transcription factor, which upregulates myostatin gene expression during skeletal muscle cell differentiation. This pathway is crucial for regulating muscle growth.

Area of Science:

  • Muscle biology
  • Molecular signaling
  • Gene regulation

Background:

  • Myostatin negatively regulates skeletal muscle growth.
  • Insulin-like Growth Factor 1 (IGF-1) influences myostatin expression via Nuclear Factor of Activated T cells (NFAT).

Purpose of the Study:

  • To investigate the role of CREB transcription factor activation by IGF-1 in myoblast differentiation.
  • To determine CREB's function in regulating myostatin gene expression.

Main Methods:

  • Cultured skeletal myoblasts were treated with IGF-1.
  • Investigated signaling pathways including IGF-1 Receptor/PI3K/PLCγ, CaMK II, ERK, and PKC.
  • Assessed myostatin mRNA levels and promoter activity.
  • Utilized siRNA-CREB transfection and pharmacological inhibitors.

Main Results:

  • IGF-1 induced CREB phosphorylation and transcriptional activation via specific signaling pathways.
  • IGF-1 increased myostatin mRNA and promoter activity in differentiated myoblasts.
  • Downregulation of CREB or inhibition of its activation pathways reduced myostatin expression.

Conclusions:

  • IGF-1 regulates myostatin gene expression through the CREB transcription factor during muscle cell differentiation.
  • This study elucidates a key molecular mechanism controlling muscle growth and differentiation.
Keywords:
CREBCalcium signalingIGF-1IP(3)Myostatin

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