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Modulation of insulin-like growth factor 1 function by C-terminal E-peptides during muscle differentiation and myofibrillogenesis

Objective

Muscle weakness and loss of muscle cytoarchitecture are associated with several myopathies, many of which still of unknown genetic cause, and with other pathologic states, such as the muscle atrophy that results from aging, cancer or cardiac infarction (cardiac cachexia). Because of the changes in our life habits and in the average life expectancy of our societies, treating muscle weakness by increasing muscle mass or by boosting the regenerative potential of muscle tissue is becoming a major goal for the clinical industry as well as for healthcare agencies. Insulin Growth Factor 1 (IGF1) can play an important role in improving muscle function during diseased states or along the aging process. In fact, it can increase the regenerative potential of muscle tissue and/or stimulate local hypertrophy, an event that ultimately requires for active remodelling of the contractile apparatus.

However, IGF1 regulation is particularly complex, since different isoforms of the pro-hormone have been described, differing in their C-terminal E-peptides. Overall, little is known about the events controlled by alternative IGF1 isoforms specifically in muscle cells, or their importance for remodelling/stability of myofibrillar apparatus. Elucidating any direct effect exerted by IGF1 E-peptides on muscle differentiation and myofibrillogenesis, or how they influence the modes of function of IGF1, is crucial for our understanding of this system and for our capacity to modulate it to attenuate age- or disease-associated muscle weakness.

We propose the following aims:
1. To characterise the events under the control of IGF1 specifically in muscle cells;
2. To assess the role of IGF1 E-peptides on muscle cells, either as direct effectors or as modulators of IGF1 function;
3. To define the contribution of IGF1 signalling to the stability and remodelling of the myofibrillar apparatus in skeletal muscle fibres.

Call for proposal

FP6-2004-MOBILITY-12
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Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Address
Meyerhofstrasse 1
Heildeberg
Germany