Fibroblast growth factor inhibits insulin-like growth factor-II (IGF-II) gene expression and increases IGF-I receptor abundance in BC3H-1 muscle cells.
Muscle is an important target tissue for insulin-like growth factor (IGF) action. We have previously reported that muscle cell differentiation is associated with down-regulation of the IGF-I receptor at the level of gene expression that is concomitant with an increase in the expression and secretion of IGF-II. Furthermore, treatment of myoblasts with IGF-II resulted in a similar decrease in IGF-I receptor mRNA abundance, suggesting an autocrine role of IGF-II in IGF-I receptor regulation. To explore further the role of IGF-II in IGF-I receptor regulation, BC3H-1 mouse muscle cells were exposed to differentiation medium in the presence of basic fibroblast growth factor (FGF), a known inhibitor of myogenic differentiation. FGF treatment of cells resulted in a 50% inhibition of IGF-II gene expression compared to that in control myoblasts and markedly inhibited IGF-II secretion. Concomitantly, FGF resulted in a 60-70% increase in IGF-I binding compared to that in control myoblasts. Scatchard analyses and studies of gene expression demonstrated that the increased IGF-I binding induced by FGF reflected parallel increases in IGF-I receptor content and mRNA abundance. These studies indicate that FGF may up-regulate IGF-I receptor expression in muscle cells through inhibition of IGF-II peptide expression and further support the concept of an autocrine role of IGF-II in IGF-I receptor regulation. In addition, these studies suggest that one mechanism by which FGF inhibits muscle cell differentiation is through inhibition of IGF-II expression.
Rosenthal
S M
SM
Department of Pediatrics, University of California, San Francisco 94143.
Brown
E J
EJ
Brunetti
A
A
Goldfine
I D
ID
D000818:Animals; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D024510:Muscle Development; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D017451:Receptors, Somatomedin
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D007335:Insulin-Like Growth Factor II