Differential regulation of IGF-I and IGF-II gene expression in skeletal muscle cells.
- Authors
- Jiao, S., Ren, H., Li, Y., Zhou, J., Duan, C., Lu, L.
- ID
- ZDB-PUB-170302-10
- 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.