Differential regulation of IGF-I and IGF-II gene expression in skeletal muscle cells

Shuang Jiao, Hongxia Ren, Yun Li, Jianfeng Zhou, Cunming Duan, Ling Lu

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume373
Issue number1-2
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • Akt
  • IGF
  • MAPK
  • Myogenesis
  • mTOR

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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