TY - JOUR
T1 - Autocrine Growth Factor Signaling by Insulin-like Growth Factor-II Mediates MyoD-stimulated Myocyte Maturation
AU - Wilson, Elizabeth M.
AU - Hsieh, Marlene M.
AU - Rotwein, Peter
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/10/17
Y1 - 2003/10/17
N2 - Skeletal muscle differentiation, maturation, and regeneration are regulated by interactions between intrinsic genetic programs controlled by myogenic transcription factors, including members of the MyoD and MEF2 families, and environmental cues mediated by hormones and growth factors. Insulin-like growth factors (IGFs) also play key roles in muscle development, and in the maintenance and repair of mature muscle, but their mechanisms of interaction with other muscle regulatory networks remain undefined. To evaluate the potential interplay between MyoD and IGF signaling pathways, we have studied muscle differentiation in C3H 10T1/2 fibroblasts acutely converted to myoblasts by quantitative infection with a recombinant adenovirus encoding mouse MyoD. In these cells, IGF-II gene and protein expression are induced as early events in differentiation, and the IGF-I receptor and downstream signaling molecules, including Akt, are rapidly activated. Interference with IGF-II production by a tetracycline-inhibited adenovirus expressing an IGF-II cDNA in the antisense orientation reversibly inhibited both production of muscle-specific structural proteins and myocyte fusion to form multinucleated myotubes. Similar results were achieved with a tetracycline-inhibited adenovirus expressing dominant-negative Akt. Our observations identify a robust autocrine amplification network in which MyoD enhances the later steps in muscle differentiation by induction of a locally acting growth factor.
AB - Skeletal muscle differentiation, maturation, and regeneration are regulated by interactions between intrinsic genetic programs controlled by myogenic transcription factors, including members of the MyoD and MEF2 families, and environmental cues mediated by hormones and growth factors. Insulin-like growth factors (IGFs) also play key roles in muscle development, and in the maintenance and repair of mature muscle, but their mechanisms of interaction with other muscle regulatory networks remain undefined. To evaluate the potential interplay between MyoD and IGF signaling pathways, we have studied muscle differentiation in C3H 10T1/2 fibroblasts acutely converted to myoblasts by quantitative infection with a recombinant adenovirus encoding mouse MyoD. In these cells, IGF-II gene and protein expression are induced as early events in differentiation, and the IGF-I receptor and downstream signaling molecules, including Akt, are rapidly activated. Interference with IGF-II production by a tetracycline-inhibited adenovirus expressing an IGF-II cDNA in the antisense orientation reversibly inhibited both production of muscle-specific structural proteins and myocyte fusion to form multinucleated myotubes. Similar results were achieved with a tetracycline-inhibited adenovirus expressing dominant-negative Akt. Our observations identify a robust autocrine amplification network in which MyoD enhances the later steps in muscle differentiation by induction of a locally acting growth factor.
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U2 - 10.1074/jbc.C300299200
DO - 10.1074/jbc.C300299200
M3 - Article
C2 - 12941952
AN - SCOPUS:0142039870
SN - 0021-9258
VL - 278
SP - 41109
EP - 41113
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 42
ER -