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Overexpression of insulin‐like growth factor‐II induces accelerated myoblast differentiation
Author(s) -
Stewart Claire E. H.,
James Payton L.,
Fant Michael E.,
Rotwein Peter
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199610)169:1<23::aid-jcp3>3.0.co;2-g
Subject(s) - myogenin , autocrine signalling , paracrine signalling , biology , myocyte , growth factor , cellular differentiation , cell culture , insulin like growth factor , c2c12 , skeletal muscle , endocrinology , insulin like growth factor 2 , medicine , cell growth , microbiology and biotechnology , myogenesis , biochemistry , receptor , gene , genetics
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 underphosphrylated 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‐5 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. © 1996 Wiley‐Liss, Inc.