Trends in Immunology
IGF-1, inflammation and stem cells: interactions during muscle regeneration
Introduction
The prevention or attenuation of muscle degeneration and weakness, both age- or disease related, have been the main focus in the field of muscle biology in the past few years. Even though much progress has been made in understanding most of the defects at the molecular level, muscular diseases are still difficult to treat. Among other factors, recent experimental models have implicated insulin-like growth factor-1 (IGF-1) as a modulator of growth and regeneration in skeletal muscle. In this review, we present the current state of the IGF-1 field, highlight its complexity at the molecular level, present the role of one of the IGF-1 isoforms, namely mIGF-1, in all phases of repair and discuss the mechanisms whereby mIGF-1 coordinates a regenerative response to muscle injury.
Section snippets
IGF-1, IGF-1 isoforms and the importance of the IGF binding proteins
IGF-1 signalling in muscle biology (Box 1) has been an interesting issue, as a result of the fact that IGF-1 induces both proliferation and differentiation via the type 1 receptor. IGF-1 has been shown to activate myoblast (see Glossary) proliferation through mitogen-activated protein kinase signalling and, subsequently, to induce differentiation via phosphatidylinositol 3-kinase (PI3-K; PtdIns3-K) activation 1, 2, 3. The PI3-K pathway is also involved in mediating muscle hypertrophy, as well
IGF-1 and muscle repair
Tissue repair occurs in four interdependent phases: degeneration, inflammation, regeneration and fibrosis. Healing can be considered as a continuous sequence of inflammation and repair, in which a variety of immune cells invade and interact with the damaged tissue 10, 11. The beneficial outcome of the regeneration process is influenced by growth and differentiation factors within the tissue, the degree of injury, and the interactions between muscle and the invading inflammatory cells (reviewed
Summary and future directions
For many years, scientists and clinicians have been searching for therapeutic avenues to help patients to improve muscle healing and to decelerate or reverse the functional losses of dystrophy and atrophy associated with ageing and neuromuscular diseases. Clinical applications of IGF-1 have been proposed but few have proceeded to human trials. An exception is the use of recombinant human IGF-1 for slowing the progressive weakness in amyotrophic lateral sclerosis patients, clinical trials of
Acknowledgements
Our work is supported by grants from the EU, the Muscular Dystrophy Association and the Leducq Foundation for Transatlantic Research. In addition, we are grateful to Antonio Musarò, Shin Woo Kang, and various members of the Rosenthal laboratory for their critical comments on the manuscript. We apologize for excluding studies that we were unable to cover as a result of space constraints.
Glossary
- Muscle-derived stem cell(s):
- a potentially new type of undifferentiated cells isolated from adult skeletal muscle on the basis of Hoechst dye exclusion [43,55,56]. These cells are considered to be distinct from the myogenic lineage, [43], or even mesenchymal cells [57], and although positive for some of the markers for hematopoietic lineage, such as CD34, and Sca-1, their exact origin is still under investigation [45,55,56]. Whether these cells are attached to the capillaries and are activated
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