Bone Fractures and the PEG-MGF Peptide
The scientific community considers the Mechano Growth Factor (MGF) peptide as a member of the IGF-1 (insulin-like growth factor) family [i]. The naturally occurring MGF, also known as IGF-1Ec, is mostly generated in the liver [ii] and is an isoform of IGF-1. The three mRNA isoforms IGF-1Ea, IGF-1Eb, and IGF-1Ec, may all be generated by transcription of the same IGF-1 gene. This suggests that MGF (or IGF-1Ec) is structurally similar to IGF-1 but has a unique E domain. Each isoform’s synthesis seems to serve a unique purpose in various tissues in response to various inputs.
Synthetic MGF is known as polyethylene glycol (PEG)-ylated MGF or PEG-MGF. Pegylation is the structural modification of a chemical by joining polyethylene glycol (PEG). Researchers speculate that although MGF may have a brief half-life unbound, it may be prolonged by several days when coupled with PEG.
Studies suggest PEG IGF-1 may potentially be more effective than recombinant IGF-1 in promoting muscle regeneration and enhancing muscular function. It was hypothesized that PEG’s low binding affinity might be to blame for the sluggish clearance time. IGF-1’s potential influence at the tissue levels is further enhanced by adding PEG to the peptide’s C terminus [iii].
PEG-MGF Peptide Overview
In order to produce the mature version of IGF-1, scientists hypothesized the presence of three IGF-1 precursor proteins. Each precursor has the same 70 amino acid residues seen in mature IGF-1, except for the amino acid sequence at the COOH terminus. One of the three precursors, IGF-1EC (MGF), was hypothesized to rise in response to muscle damage 4 in the late 1990s and early 2000s.
Since then, many attempts [iii] have been made to extract and synthetically produce (PEG)-ylated MGF to alter and, perhaps, enhance the potential impact and activity of the peptide. Research suggests that in conditions of muscular stress, such as during intense physical activity, the mature IGF-1 may undergo splicing in response to stress, producing and releasing an isoform known as IGF-1EC, or Mechano Growth Factor (MGF). [iv]
One line of the study suggests the amino acid sequence linked to the COOH terminus of MGF may become activated and enhance cell proliferation in muscle stem cells. Studies suggested that introducing PEG-MGF might promote the growth of C2C12 muscle cells and myoblasts. It was concluded from these findings that the MGF peptide may be both physiologically active and inert. Researchers speculate PEG-MGF may prolong the action of standard MGF. Now, the peptide is being investigated for the following possible effects:
- Possibility of Muscle Reconstruction
- Potential capacity for generating new muscle tissue
- Possibility of neuroprotection for the brain and nervous system.
- Possible heart-protective properties
- Tissue repair potential
- Possibilities in repairing bone damage
PEG-MGF Peptide and Muscle
The primary purpose of this investigation [v] was to analyze the potential effects of MGF on recovering muscle tissue and wounds. Muscle contusion–induced macrophage depletion–selected animals were used in this experiment, then MGF was presented to the mice. Researchers hypothesized that MGF might stimulate muscle healing in injured areas based on extensive post-study evaluations. The findings suggested the production of inflammatory cytokines, chemokines, and stress factors appeared to be reduced, and the rate of fibrosis in the contused muscles decreased after MGF presentation.
PEG-MGF Peptide and Heart Muscle
The primary purpose of this investigation [vi] was to examine the potential impact of MGF on cardiac muscles experiencing programmed cell death due to hypoxia. Cellular apoptosis was generated in rats by experimental induction of hypoxia with just 1% oxygen supply. After presenting the peptide to the test subjects, the researchers suggested that it seemed to cause greater migration of stem cells to the heart, which may have suppressed apoptosis.
PEG-MGF Peptide and Bone
The primary purpose of this investigation [vii] was to examine the possible action of MGF on bone damage. Experimentally inducing a 5-mm bone deficiency in 27 rabbits, the animals were split into three groups and given either MGF or a placebo for five days. After the study, the researchers performed a histological analysis of the bone tissues and found that the placebo tissue seemed to look the worst, while the bone tissue given MGF appeared to look the best.
PEG-MGF Peptide and the Brain
Researchers have done many experiments in mice [viii] in which MGF levels were artificially raised to observe the possible action of high MGF concentrations on brain cells. Mice were bred to cause a permanent increase in MGF production in the hippocampus. The hippocampal region is thought to be pivotal in controlling the neurogenesis process. It seemed that excessive MGF synthesis might lead to elevated levels of BrdU, a biological marker thought to be indicative of proliferative activity.
In independent research, mice were developed to produce MGF conditionally at 1, 3, and 12 months. After 2 years, the subjects’ behavior and biological reactions were analyzed. The BrdU and neurogenesis levels in these mice appeared much higher than average.
PEG-MGF peptide is still being actively researched. Its availability for sale online is restricted to research and educational institutes. PEG-MGF and other compounds discussed here are not approved for personal use and are strictly prohibited from human consumption of any type. A reputable supplier for licensed professionals is Core Peptides. This article is intended only for informational purposes.
[i] 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. https://pubmed.ncbi.nlm.nih.gov/19567392/
[ii] Zabłocka, B., Goldspink, P. H., Goldspink, G., & Górecki, D. C. (2012). Mechano-Growth Factor: an important cog or a loose screw in the repair machinery? Frontiers in endocrinology, 3, 131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485521/
[iii] Janssen, J. A., Hofland, L. J., Strasburger, C. J., van den Dungen, E. S., & Thevis, M. (2016). Potency of Full-Length MGF to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations. PloS one, 11(3), e0150453. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798685/
[iv] Rotwein P. (2014). Editorial: the fall of mechanogrowth factor?. Molecular endocrinology (Baltimore, Md.), 28(2), 155–156. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896639/
[v] Liu X, Zeng Z, Zhao L, Chen P, Xiao W. Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion Could Be Partly Ameliorated by MGF Injection. Front Physiol. 2019 May 17;10:601. https://pubmed.ncbi.nlm.nih.gov/31164836/
[vi] Doroudian G, Pinney J, Ayala P, Los T, Desai TA, Russell B. Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014 Oct;16(5):705-15. https://pubmed.ncbi.nlm.nih.gov/24908137/
[vii] Deng M, Zhang B, Wang K, Liu F, Xiao H, Zhao J, Liu P, Li Y, Lin F, Wang Y. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. Int Orthop. 2011 Jul;35(7):1099-106. https://pubmed.ncbi.nlm.nih.gov/21057789/
[viii] Alec Walker. Hearts and Minds of Mice and Men: Mechano Growth Factor a new tool in the battle against age-related neuron loss? 20 Jul 2017. https://blogs.biomedcentral.com/on-biology/2017/07/20/hearts-minds-mice-men-mechano-growth-factor-new-tool-battle-age-related-neuron-loss/