MGF or IGF-1Ec
Mechano growth factor, also known as MGF or IGF-1Ec, is a locally expressed splice variant of IGF-1. It is generated on a cellular level and plays a key role in the growth factor cascades of pubery and post-exercise. MGF binds to IGF receptors and acts as a cell proliferator primarily:
The physiological function of a recently cloned splice variant of insulin-like growth factor-I (IGF-I; mechano growth factor (MGF)) was studied using an in vitro cell model. Unlike mature IGF-I, the distinct E domain of MGF inhibits terminal differentiation whilst increasing myoblast proliferation. Blocking the IGF-I receptor with a specific antibody indicated that the function of MGF E domain is mediated via a different receptor. The results provide a basis for localized tissue adaptation and helps explain why loss of muscle mass occurs in the elderly and in dystrophic muscle in which MGF production is markedly affected.
Proliferation of cells refers to the growth portion of a cell's life, which occurs before differentiation. After differentiation is complete, a cell is considered specialized.
MGF does not occur in a vacuum within the body; in vitro MGF, or exogenous MGF, has a different effect on the body from endogenously released MGF in vivo which occurs as part of a growth factor cascade in the body:
The predominant form, IGF-1Ea is a circulating factor while two others, IGF-1Eb and IGF-1Ec (MGF), are mostly expressed in different tissues or in response to various stimuli and show some preferences with respect to the signal transduction pathways they activate. In skeletal muscle specific forms of IGF-1 play a role in development and growth and in addition to these physiological roles IGF-1 functions in the damaged muscle. IGF-1 is also important for the developing and adult brain and can reduce neuronal death caused by different types of injuries. Like many other peptide hormones IGF-1 originates from a precursor pro-hormone that undergoes extensive post-translational modifications. Processing liberates the mature peptide, which acts via the specific IGF-1 receptor but additional short peptides can arise from both N- and C-termini of various IGF-1 isoforms.
MGF has recently been identified as one of the most important IGF isoforms with regard to hypertrophy in response to a mechanical overload stimulus:
These IGF-1 mRNA transcripts code different isoforms of the precursor peptide of IGF-1 (IGF-1Ea, IGF-1Eb and IGF-1Ec or MGF in human skeletal muscle), which also undergo post-translational modification. There is increasing interest in differential expression and implication of IGF-1 isoforms in the regulation of muscle fiber regeneration and hypertrophy following mechanical overloading and damage. The identification of a locally expressed, loading- or damage-sensitive IGF-1 isoform in skeletal muscle was one of the most attractive developments in the context of the autocrine/paracrine actions of IGF-1. The concept that the competing processes of cellular proliferation and differentiation and the increased protein synthesis required for muscle repair or hypertrophic adaptation are regulated by a differential expression and by distinct roles of IGF-1 isoforms is discussed in the present review.
Fortunately, data is available from studies performed on healthy human volunteers regarding the local expression of MGF in response to weight training:
Different insulin-like growth factor-1 (IGF-1) isoforms, namely IGF-1Ea, IGF-1Eb and IGF-1Ec (MGF), have been proposed to have various functions in muscle repair and growth. To gain insight into the potentially differential actions of IGF-1 isoforms in the regulation of muscle regeneration, we assessed the time course of their expressions at both mRNA and protein levels after exercise-induced muscle damage in humans. In addition, we characterized mature IGF-1 and synthetic MGF E peptide signaling in C2C12 myoblast-like cells in vitro. Ten healthy male volunteers were subjected to exercise-induced muscle damage and biopsy samples were taken from the exercised muscles....we conclude that the differential expression profile of IGF-1 isoforms in vivo and the possible IGF-1R - independent MGF E peptide signaling in skeletal muscle-like cells in vitro support the notion that tissue-specific mRNA expression of MGF isoform produces mature IGF-1 and MGF E peptides which possibly act as distinct mitogens in skeletal muscle regeneration.
In other words, MGF plays a vital role as part of a cascade in skeletal muscle regeneration in response to externally induced muscle damage.
Dai et al's observations on MGF as a neuroprotectant, growth factor in response to external stimuli, and a potential medical treatment (when administered exogenously) represent an exciting synthesis of new data:
insulin-like growth factor I (IGF-I) is an important growth factor for embryonic development, postnatal growth, tissue repair and maintenance of homeostasis. IGF-I functions and regulations are complex and tissue-specific. IGF-I mediates growth hormone signaling to target tissues during growth, but many IGF-I variants have been discovered, resulting in complex models to describe IGF-I function and regulation. Mechano-growth factor (MGF) is an alternative splicing variant of IGF-I and serves as a local tissue repair factor that responds to changes in physiological conditions or environmental stimuli. MGF expression is significantly increased in muscle, bone and tendon following damage resulting from mechanical stimuli and in the brain and heart following ischemia. MGF has been shown to activate satellite cells in muscle resulting in hypertrophy or regeneration, and functions as a neuroprotectant in brain ischemia. Both expression and processing of this IGF-I variant are tissue specific, but the functional mechanism is poorly understood. MGF and its short derivative have been examined as a potential therapy for muscular dystrophy and cerebral hypoxia-ischemia using experimental animals. Although the unique mode of action of MGF has been identified, the details remain elusive. Here we review the expression and regulation of MGF and the function of this IGF-I isoform in tissue protection.
Bachl discusses MGF and similar growth factors as potential medical boons, but also expresses concern over the "doping potential," i.e. human performance enhancement potential, of the research chemicals: "These GFs not only have the potential to be used to cure injuries but also are being in the centre of interest for doping abusers and are a powerful yet not fully understood technique to gain performance."
Wilborn et al found that using between 60-85% of 1-rep-max stimulates maximal release of MHCs (myosin heavy chain isoforms), of which IGF-1ec is considered a part.
In a separate study, Wilborn et al found that MGF may have potential, as a protector of dopamine neurons, in the treatment of Parkinson's or other neurological disease:
To assess potential efficacy of mechano growth factor (MGF) for chronic neurodegenerative disorders, we studied whether MGF protects dopamine (DA) neurons subjected to neurotoxic stress.....This report is the first to demonstrate that a small peptide, MGF24, upregulates HO-1, an important cell defense mediator, and protects DA cells, suggesting new strategies for neuroprotection in Parkinson's disease.
Goldspink expresses the medical community's perennial concern with "doping" and use/abuse of growth factors and other such research chemicals by bodybuilders:
Emerging molecular techniques have made it possible to gain a better understanding of the growth factor genes involved and how they are activated by physical activity including the IGF-I gene that can be spliced to give rise to different isoforms, one of which is called MGF that activates muscle progenitor cells that provide the extra nuclei required for muscle hypertrophy, repair and maintenance. This fact that MGF 'kick starts' the hypertrophy process clearly has potential for abuse and has already attracted the attention of body builders.
Wackerhage et al give insight into the larger cascade of growth factors of which MGF is an integral part:
Progressive high-resistance exercise with 8-12 repetitions per set to near failure for beginners and 1-12 repetitions for athletes will increase muscle protein synthesis for up to 72 h; approx. 20 g of protein, especially when ingested directly after exercise, will promote high growth by elevating protein synthesis above breakdown. Muscle growth is regulated by signal transduction pathways that sense and compute local and systemic signals and regulate various cellular functions. The main signalling mechanisms are the phosphorylation of serine, threonine and tyrosine residues by kinases and their dephosphorylation by phosphatases. Muscle growth is stimulated by the mTOR (mammalian target of rapamycin) system, which senses (i) IGF-1 (insulin-like growth factor 1)/MGF (mechano-growth factor)/insulin and/or (ii) mechanical signals, (iii) amino acids and (iv) the energetic state of the muscle, and regulates protein synthesis accordingly. The action of the mTOR system is opposed by myostatin-Smad signalling which inhibits muscle growth via gene transcription.
In a recent study, the finding that systemic IGF-1 expression is increased by rHGH expression in healthy young men was contradicted:
Although rhGH administration has an effect on liver IGF-I expression, as shown by increase in circulating IGF-I, muscle IGF-I expression is unaffected in young healthy subjects with normal GH profile. The findings contrast with those of a previous study in which GH deficient elderly men showed higher muscle IGF-I 3' splice variant levels following rhGH administration with and without resistance training. Unlike in the liver, muscle Class1 and 2 IGF-I expression do not change significantly following administration of rhGH.
Yang SY, Goldspink G. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett. 2002 Jul 3;522(1-3):156-60.
Górecki DC, Beresewicz M, Zabłocka B. Neuroprotective effects of short peptides derived from the Insulin-like growth factor 1. Neurochem Int. 2007 Dec;51(8):451-8.
Philippou A, Maridaki M, Halapas A, Koutsilieris M. The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology. In Vivo. 2007 Jan-Feb;21(1):45-54.
Philippou A, Papageorgiou E, Bogdanis G, Halapas A, Sourla A, Maridaki M, Pissimissis N, Koutsilieris M. Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro. In Vivo. 2009 Jul-Aug;23(4):567-75.
Dai Z, Wu F, Yeung EW, Li Y. IGF-IEc expression, regulation and biological function in different tissues. Growth Horm IGF Res. 2010 May 20.
Bachl N, Derman W, Engebretsen L, Goldspink G, Kinzlbauer M, Tschan H, Volpi P, Venter D, Wessner B. Therapeutic use of growth factors in the musculoskeletal system in sports-related injuries. J Sports Med Phys Fitness. 2009 Dec;49(4):346-57.
Wilborn CD, Taylor LW, Greenwood M, Kreider RB, Willoughby DS. Effects of different intensities of resistance exercise on regulators of myogenesis. J Strength Cond Res. 2009 Nov;23(8):2179-87.
Quesada A, Micevych P, Handforth A. C-terminal mechano growth factor protects dopamine neurons: a novel peptide that induces heme oxygenase-1. Exp Neurol. 2009 Dec;220(2):255-66.
Goldspink G, Wessner B, Bachl N. Growth factors, muscle function and doping. Curr Opin Pharmacol. 2008 Jun;8(3):352-7.
Wackerhage H, Ratkevicius A. Signal transduction pathways that regulate muscle growth. Essays Biochem. 2008;44:99-108.
Aperghis M, Velloso CP, Hameed M, Brothwood T, Bradley L, Bouloux PM, Harridge SD, Goldspink G. Serum IGF-I levels and IGF-I gene splicing in muscle of healthy young males receiving rhGH. Growth Horm IGF Res. 2009 Feb;19(1):61-7.
*The latter article is intended for educational / informational purposes only. THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. Bodily introduction of any kind into humans or animals is strictly forbidden by law.