LakeMountD
Doctor Science
- Awards
- 1
Muscle-specific inactivation of the IGF-I receptor induces compensatory hyperplasia in skeletal muscle
Ana M. Fernández1, Joëlle Dupont1, Roger P. Farrar2, Sukho Lee2, Bethel Stannard1 and Derek Le Roith1
1 Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
2 Department of Kinesiology, University of Texas at Austin, Austin, Texas, USA
Address correspondence to: Derek Le Roith, Molecular and Cellular Physiology Section, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 8D12, Bethesda, Maryland 20892-1758, USA. Phone: (301) 496-8090; Fax: (301) 480-4386; E-mail: [email protected].
Received for publication June 13, 2001, and accepted in revised form December 28, 2001.
During the development of skeletal muscle, myoblasts withdraw from the cell cycle and differentiate into myotubes. The insulin-like growth factors IGF-I and IGF-II, through their cognate tyrosine kinase receptor (IGF-I receptor), are known to play a role in this process. After withdrawal of myoblasts from the cell cycle, IGF-I promotes muscle differentiation by inducing the expression or activity of myogenic regulatory factors (MyoD, myogenin) and effectors (p21). However, little is known about the intracellular mechanisms by which the IGF-I system regulates these factors during the process of myogenesis. Here we show that MKR mice, which express a dominant negative IGF-I receptor specifically in skeletal muscle, have marked muscle hypoplasia from birth to 3 weeks of age. This hypoplasia occurs concomitantly with a decrease in ERK immunoreactivity levels and decreases in MyoD and myogenin expression. BrdU immunocytochemistry showed a compensatory hyperplasia as MKR mice grew to adulthood. Interestingly, hyperplasia occurred concomitantly with an increase in p38, MyoD, myogenin, and p21 immunoreactivity levels, as well as a decrease in Twist levels. These findings suggest that regulation of these cellular elements by IGF-I may play a role in the development and differentiation of skeletal muscle in vivo.
Ana M. Fernández1, Joëlle Dupont1, Roger P. Farrar2, Sukho Lee2, Bethel Stannard1 and Derek Le Roith1
1 Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
2 Department of Kinesiology, University of Texas at Austin, Austin, Texas, USA
Address correspondence to: Derek Le Roith, Molecular and Cellular Physiology Section, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 8D12, Bethesda, Maryland 20892-1758, USA. Phone: (301) 496-8090; Fax: (301) 480-4386; E-mail: [email protected].
Received for publication June 13, 2001, and accepted in revised form December 28, 2001.
During the development of skeletal muscle, myoblasts withdraw from the cell cycle and differentiate into myotubes. The insulin-like growth factors IGF-I and IGF-II, through their cognate tyrosine kinase receptor (IGF-I receptor), are known to play a role in this process. After withdrawal of myoblasts from the cell cycle, IGF-I promotes muscle differentiation by inducing the expression or activity of myogenic regulatory factors (MyoD, myogenin) and effectors (p21). However, little is known about the intracellular mechanisms by which the IGF-I system regulates these factors during the process of myogenesis. Here we show that MKR mice, which express a dominant negative IGF-I receptor specifically in skeletal muscle, have marked muscle hypoplasia from birth to 3 weeks of age. This hypoplasia occurs concomitantly with a decrease in ERK immunoreactivity levels and decreases in MyoD and myogenin expression. BrdU immunocytochemistry showed a compensatory hyperplasia as MKR mice grew to adulthood. Interestingly, hyperplasia occurred concomitantly with an increase in p38, MyoD, myogenin, and p21 immunoreactivity levels, as well as a decrease in Twist levels. These findings suggest that regulation of these cellular elements by IGF-I may play a role in the development and differentiation of skeletal muscle in vivo.
