Overexpression of insulin-like growth factor-II induces accelerated myoblast differentiation

Claire E H Stewart, Payton L. James, Michael E. Fant, Peter Rotwein

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Previous studies have shown that exogenous insulin-like growth factors (IGFs) can stimulate the terminal differentiation of skeletal myoblasts in culture and have established a correlation between the rate and the extent of IGF-II secretion by muscle cell lines and the rate of biochemical and morphological differentiation. To investigate the hypothesis that autocrine secretion of IGF-II plays a critical role in stimulating spontaneous myogenic differentiation in vitro, we have established C2 muscle cell lines that stably express a mouse IGF-II cDNA under control of the strong, constitutively active Moloney sarcoma virus promoter, enabling us to study directly the effects of IGF-II overproduction. Similar to observations with other muscle cell lines, IGF-II overexpressing myoblasts proliferated normally in growth medium containing 20% fetal serum, but they underwent enhanced differentiation compared with controls when incubated in low-serum differentiation medium. Accelerated differentiation of IGF-II overexpressing C2 cells was preceded by the rapid induction of myogenin mRNA and protein expression (within 1 h, compared with 24-48 h in controls) and was accompanied by an enhanced proportion of the retinoblastoma protein in an underphosphorylated and potentially active form, by a marked increase in activity of the muscle-specific enzyme, creatine phosphokinase, by extensive myotube formation by 48 h, and by elevated secretion of IGF binding protein-S when compared with controls. These results confirm a role for IGF-II as an autocrine/paracrine differentiation factor for skeletal myoblasts, and they define a model cell system that will be useful in determining the biochemical mechanisms of IGF action in cellular differentiation.

Original languageEnglish (US)
Pages (from-to)23-32
Number of pages10
JournalJournal of Cellular Physiology
Volume169
Issue number1
DOIs
StatePublished - Oct 1996
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor II
Myoblasts
Muscle
Skeletal Myoblasts
Muscle Cells
Cells
Somatomedins
Cell Line
Moloney murine sarcoma virus
Myogenin
Insulin-Like Growth Factor Binding Proteins
Retinoblastoma Protein
Protein S
Serum-Free Culture Media
Skeletal Muscle Fibers
Creatine Kinase
Viruses
Complementary DNA
Muscles
Messenger RNA

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Overexpression of insulin-like growth factor-II induces accelerated myoblast differentiation. / Stewart, Claire E H; James, Payton L.; Fant, Michael E.; Rotwein, Peter.

In: Journal of Cellular Physiology, Vol. 169, No. 1, 10.1996, p. 23-32.

Research output: Contribution to journalArticle

Stewart, Claire E H ; James, Payton L. ; Fant, Michael E. ; Rotwein, Peter. / Overexpression of insulin-like growth factor-II induces accelerated myoblast differentiation. In: Journal of Cellular Physiology. 1996 ; Vol. 169, No. 1. pp. 23-32.
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