ZFIN ID: ZDB-PUB-170302-10
Differential regulation of IGF-I and IGF-II gene expression in skeletal muscle cells.
Jiao, S., Ren, H., Li, Y., Zhou, J., Duan, C., Lu, L.
Date: 2013
Source: Molecular and cellular biochemistry   373(1): 107-113 (Journal)
Registered Authors: Duan, Cunming, Zhou, Jianfeng
Keywords: Akt, IGF, MAPK, mTOR, Myogenesis
MeSH Terms:
  • Animals
  • Cell Line
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Feedback, Physiological
  • Gene Expression Regulation
  • Insulin-Like Growth Factor I/genetics*
  • Insulin-Like Growth Factor I/metabolism
  • Insulin-Like Growth Factor II/genetics*
  • Insulin-Like Growth Factor II/metabolism
  • MAP Kinase Signaling System
  • Mice
  • Muscle Fibers, Skeletal/metabolism*
  • Phosphatidylinositol 3-Kinases/metabolism
  • Proto-Oncogene Proteins c-akt/metabolism
  • TOR Serine-Threonine Kinases/metabolism
  • Transcription, Genetic
  • Transcriptional Activation*
  • p38 Mitogen-Activated Protein Kinases/metabolism
PubMed: 23054195 Full text @ Mol. Cell. Biochem.

Insulin-like growth factor (IGF)-I and IGF-II play major roles in the regulation of skeletal muscle growth and differentiation, and both are locally expressed in muscle cells. Recent studies have demonstrated that IGF-II up-regulates its own gene expression during myogenesis and this auto-regulatory loop is critical for muscle differentiation. How local IGF-I is regulated in this process is unclear. Here, we report that while IGF-II up-regulated its own gene expression, it suppressed IGF-I gene expression during myogenesis. These opposite effects of IGF-II on IGF-I and IGF-II genes expression were time dependent and dose dependent. It has been shown that IGFs activate the PI3K-Akt-mTOR, p38 MAPK, and Erk1/2 MAPK pathways. In myoblasts, we examined their role(s) in mediating the opposite effects of IGF-II. Our results showed that both the PI3K-Akt-mTOR and p38 MAPK pathways played critical roles in increasing IGF-II mRNA expression. In contrast, mTOR was required for down-regulating the IGF-I gene expression by IGF-II. In addition, Akt, Erk1/2 MAPK, and p38 MAPK pathways were also involved in the regulation of basal levels of IGF-I and IGF-II genes during myogenesis. These findings reveal a previously unrecognized negative feedback mechanism and extend our knowledge of IGF-I and IGF-II gene expression and regulation during myogenesis.