Mourkioti F, Rosenthal NIGF-1, inflammation and stem cells: interactions during muscle regeneration. Trends Immunol 26: 535-542
Insulin-like growth factor-I (IGF-1) is an important mediator in numerous developmental processes, such as proliferation, differentiation, survival, growth, apoptosis and regeneration. Mouse genetics have provided important insights into the signalling mechanisms that are necessary for the coordination of muscle repair. Recent studies on the role of IGF-1 in the promotion of cell recruitment to the injured muscle and the subsequent resolution of the inflammatory response have unveiled new perspectives into local repair mechanisms.
[Show abstract] [Hide abstract] ABSTRACT: Ageing is characterised by progressive deterioration of physiological systems and the loss of skeletal muscle mass is one of the most recognisable, leading to muscle weakness and mobility impairments. This review highlights interactions between the immune system and skeletal muscle precursor cells (widely termed satellite cells or myoblasts) to influence satellite cell behaviour during muscle regeneration after injury, and outlines deficits associated with ageing. Resident neutrophils and macrophages in skeletal muscle become activated when muscle fibres are damaged via stimuli (e.g. contusions, strains, avulsions, hyperextensions, ruptures) and release high concentrations of cytokines, chemokines and growth factors into the microenvironment. These localised responses serve to attract additional immune cells which can reach in excess of 1×10(5) immune cell/mm(3) of skeletal muscle in order to orchestrate the repair process. T-cells have a delayed response, reaching peak activation roughly 4days after the initial damage. The cytokines and growth factors released by activated T-cells play a key role in muscle satellite cell proliferation and migration, although the precise mechanisms of these interactions remain unclear. T-cells in older people display limited ability to activate satellite cell proliferation and migration which is likely to contribute to insufficient muscle repair and, consequently, muscle wasting and weakness. If the factors released by T-cells to activate satellite cells can be identified, it may be possible to develop therapeutic agents to enhance muscle regeneration and reduce the impact of muscle wasting during ageing and disease.0Comments 0Citations
- "This cytokine transference diminishes the proinflammatory response and supports the differentiation of myofibres (Deng et al., 2012), thereby positively influencing the regenerative process (Tidball, 2005; Arnold et al., 2007 ). This is in part linked to insulin-like growth factor I (IGF-I), a protein known for its growth-promoting properties and anabolic-inducing effects through the up-regulation of myogenic regulatory factors (MRFs) (Chakravarthy et al., 2000; Mourkioti and Rosenthal, 2005; Xu and Wu, 2000 ). Importantly, IGF-I is also secreted by M2 macrophages during muscle regeneration (Tonkin et al., 2015; Tidball and Welc, 2015). "
[Show abstract] [Hide abstract] ABSTRACT: The study of factors that regulate the survival, proliferation, and differentiation of neural precursor cells (NPCs) is essential to understand neural development as well as brain regeneration. The Nuclear Factor of Activated T Cells (NFAT) is a family of transcription factors that can affect these processes besides playing key roles during development, such as stimulating axonal growth in neurons, maturation of immune system cells, heart valve formation, and differentiation of skeletal muscle and bone. Interestingly, NFAT signaling can also promote cell differentiation in adults, participating in tissue regeneration. The goal of the present study is to evaluate the expression of NFAT isoforms in NPCs, and to investigate its possible role in NPC survival, proliferation, migration, and differentiation. Our findings indicate that NFAT proteins are active not only in neurogenic brain regions such as hippocampus and subventricular zone (SVZ), but also in cultured NPCs. The inhibition of NFAT activation with the peptide VIVIT reduced neurosphere size and cell density in NPC cultures by decreasing proliferation and increasing cell death. VIVIT also decreased NPC migration and differentiation of astrocytes and neurons from NPCs. In addition, we identified NFATc3 as a predominant NFAT isoform in NPC cultures, finding that a constitutively-active form of NFATc3 expressed by adenoviral infection reduces NPC proliferation, stimulates migration, and is a potent inducer of NPC differentiation into astrocytes and neurons. In summary, our work uncovers active roles for NFAT signaling in NPC survival, proliferation and differentiation, and highlights its therapeutic potential for tissue regeneration. GLIA 2014. © 2015 Wiley Periodicals, Inc.0Comments 1Citation
- "In this regard, there are reports supporting the cooperation between NFAT and NF-kappa B signaling pathways in processes such as the regulation of T-cell proliferation, maturation, and activation (Macian, 2005). In addition, insulin-like growth factor I (IGF-1) has multiple effects during tissue development and regeneration , and there is evidence of NFAT activation in response to IGF-1 stimulation in tissues such as muscle (Mourkioti and Rosenthal, 2005; Valdes et al., 2013). In any case, further work will be necessary to clarify whether the NFAT effects on NPCs described in our study implicate Src-FAK, Wnt/b-catenin, NFkappa B, or IGF-1, among other signaling events. "
[Show abstract] [Hide abstract] ABSTRACT: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and young adults. Several recent studies have shed new light on the alterations in signalling pathways and the downstream effects of these pathway alterations in RMS. Many of these effects converge on the fibroblast growth factor and insulin-like growth-factor pathways. These new findings improve the current understanding of RMS, thus offering novel potential therapeutic targets and strategies that may improve the outcome for patients with RMS.British Journal of Cancer advance online publication, 11 September 2014; doi:10.1038/bjc.2014.471 www.bjcancer.com.0Comments 1Citation
- "Insulin-like growth factor is necessary for FGF-induced proliferation in other cells (Arsenijevic et al, 2001), suggesting that the signalling pathways may be interconnected in RMS cells as well. In normal skeletal muscle, IGF has both a pro-proliferative and pro-differentiation effect on cells (Mourkioti and Rosenthal, 2005 ), which suggests that the prodifferentiation function of IGF is blocked in RMS cells. The precise role of IGF in RMS cells is unclear, but IGF clearly promotes the proliferation of RMS cells and blocks to IGF signaling suppress the growth of RMS cells in vivo. "