PEGylated MGF: Skeletal Muscle Cell Regeneration and Cardiac Protection

Pegylated MGF (Pegylated Mechano-Growth Factor) is a truncated isoform of insulin-like growth factor 1 (IGF-1), structurally modified to support stability and bioavailability. Pegylated MGF is speculated to play a critical role in promoting myoblast proliferation and differentiation, processes considered to be essential for muscular tissue repair and growth. Initial research suggests that Pegylated MGF may contribute to better-supported endurance, immune modulation, lipid profile regulation, and reduction in adipose tissue stores. Additionally, Pegylated MGF’s potential to accelerate wound healing through immune function support has been a subject of growing interest to researchers in this field.⁽¹⁾

Structurally, Pegylated MGF consists of a primary sequence corresponding to mechano-growth factor (MGF), conjugated with polyethylene glycol (PEG) to extend its half-life. Research suggests that endogenous MGF has a limited half-life, rapidly degrading in the bloodstream. Pegylation, the process of attaching polyethylene glycol to the MGF molecule, offsets this limitation by stabilizing the molecule, allowing for systemic action without significant degradation. This extended half-life may support Pegylated MGF’s potential capacity to stimulate muscular tissue recovery, and is believed to contribute to its potential research implications relevant to muscular tissue repair as well as metabolic regulation.⁽²⁾ The molecular formula of Pegylated MGF is C121H200N42O39, also referred to by researchers as PEG IGF-1 Ec and PEG myotrophin.

 

Mechanism of Action

The mechanism underlying PEG-MGF’s activity is suggested to involve the stimulation of myoblast proliferation and subsequent differentiation, which is deemed critical for muscular tissue regeneration. By binding to IGF-1 receptors, Pegylated MGF appears to initiate intracellular signaling cascades that promote cellular growth and repair. Pegylation, which mitigates renal clearance and prolongs the peptide’s circulation time,⁽³⁾ is said to extend bioavailability as well as reduce immunogenicity, enabling Pegylated MGF to exert its effects over an extended period.⁽²⁾

 

Research

Pegylated MGF Peptide and Cardiac Muscular Tissue Repair

Studies suggest that mechano-growth factor (MGF) may inhibit cardiomyocyte apoptosis following hypoxic injury. Research suggests that MGF may promote cardiac stem cell recruitment to the site of myocardial damage, potentially facilitating tissue regeneration and repair post-myocardial infarction. In preclinical laboratory settings, murine models introduced to MGF within eight hours of hypoxia reportedly exhibited reduced cellular apoptosis and increased stem cell mobilization compared to untreated controls.⁽⁴⁾

Dr. Doroudian, the lead investigator of the study, hypothesizes in his observations that rod-based delivery systems may provide a targeted, sustained-release mechanism for MGF, optimizing localized effects in ischemic cardiac tissue. Parallel investigations by researchers in Dr. Doroudian’s field appear to suggest similar findings – including the idea that localized Pegylated MGF introduction may hypothetically lend support to post-infarction cardiac function by attenuating pathological hypertrophy. Murine models receiving Pegylated MGF reportedly displayed better-supported hemodynamic profiles and reduced adverse cardiac remodeling relative to unexposed counterparts.⁽⁵⁾

Additionally, researchers report that MGF introduction during acute myocardial infarction may decrease cardiomyocyte injury by up to 35%, further supporting the peptide’s potential in mitigating ischemia-induced cardiac damage.⁽⁵⁾ These findings underscore the peptide’s capacity to modulate cellular responses following myocardial injury, suggesting its potential role in future regenerative studies targeting cardiac pathophysiology.

Pegylated MGF Peptide and Skeletal Muscle Cells

Injuries to skeletal muscle tissue often necessitate surgical intervention. Preclinical investigations utilizing murine models suggest that “the impairment of skeletal muscle regeneration induced by macrophage depletion [may] be partly ameliorated by MGF [exposure] and that inflammatory cytokines, oxidative stress factors, chemokines, and MMP may be involved in this process.”⁽⁶⁾

Another research hypothesizes that MGF modulates inflammatory responses, supporting macrophage and neutrophil recruitment to injury sites. These findings align with other similar data suggesting that exercise-induced muscular tissue damage triggers the release of IGF-1Ea and IGF-1Eb, isoforms closely associated with MGF activity.⁽⁷⁾

Further studies by an international consortium of endocrinology researchers suggest that MGF activates the insulin-like growth factor 1 receptor (IGF-1R) with comparable efficacy to IGF-1. Activation of IGF-1R has been correlated with better-supported lean muscular tissue mass, better-supported metabolic efficiency, and potential anti-cellular aging effects, suggesting that Pegylated MGF may replicate IGF-1’s anabolic and reparative properties, thereby promoting muscle cell regeneration and optimizing lipid metabolism.⁽⁸⁾

In murine models, the introduction of MGF resulted in a 25% increase in the mean diameter of muscular tissue fibers, particularly in research models engaged in physical activity. The study’s researchers report the suggested limitations of direct intramuscular exposure, emphasizing the need for localized delivery to each group of muscular tissue targeted for hypertrophy.⁽⁹⁾ Pegylation is reportedly suggested to address this challenge by extending the peptide’s circulatory half-life, enabling systemic exposure via experimentation on research models, and circumventing the necessity for multiple localized concentrations.

Pegylated MGF Peptide and Bone Repair and Growth

Preclinical studies in rabbits suggest that Pegylated MGF supports bone repair by stimulating osteoblast proliferation, the primary cells involved in bone mineralization. Rabbits receiving elevated concentrations of MGF reportedly indicated accelerated healing, achieving comparable bone regeneration at four weeks that control groups exhibited at six weeks.⁽¹⁰⁾

These findings suggest the potential role of Pegylated MGF in promoting skeletal repair. They may inform future strategies to expedite bone healing and minimize the duration of immobilization required for recovery.

Pegylated MGF Peptide and Cartilage Protection

Research on experimental models suggests that MGF augments chondrocyte activity, which is essential for maintaining cartilage integrity and facilitating matrix deposition. In murine studies, MGF has been reportedly observed to support chondrocyte migration from bone into cartilaginous regions, which researchers believe may contribute to additional tissue repair.⁽¹⁰⁾ Pegylated MGF’s extended half-life is speculated to present a strategic advantage in this context, as introduction may provide prolonged effects within joint spaces where a one-time introduction of Pegylated MGF may exert sustained chondroprotective effects, contrasting with the transient activity observed with standard MGF, which typically persists for minutes to hours.

Pegylated MGF Peptide and Maxillofacial Regeneration

In vitro research involving periodontal ligament cells from research models suggests that Pegylated MGF may support osteogenic differentiation and upregulate matrix metalloproteinases MMP-1 and MMP-2. These proteins play critical roles in ligament repair, facilitating the reattachment of teeth to alveolar bone following trauma. Preliminary findings⁽¹¹⁾ suggest that Pegylated MGF may present an alternative to invasive dental procedures, potentially preserving endogenous dentition post-injury. Further, there is emerging speculation that Pegylated MGF might support outcomes in cases of tooth avulsion by supporting periodontal ligament regeneration after re-implantation.

Pegylated MGF Peptide and Neuroprotective effects

Based on the study investigating the prolonged effects of elevated mechano-growth factor (MGF) levels in the brain and central nervous system, it is suggested that increased MGF expression may mitigate cellular age-related neuronal degeneration, contributing to sustained cognitive function and prolonged peak cognitive performance in murine models. Notably, the research appears to suggest that the neuroprotective efficacy of MGF appears to correlate with cellular age, as earlier MGF overexpression yielded both immediate and long-term support for cognitive outcomes.

Further studies indicate that MGF exposure may “have an important neuroprotective function” as it attenuates muscular tissue weakness and reduces motor neuron loss in amyotrophic lateral sclerosis (ALS) murine models.⁽¹²⁾ Preliminary data suggest that MGF may influence neuromuscular stability, potentially delaying disease progression and preserving motor function.

 
NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

 

References:

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2. Hamley, I. W, “PEG−Peptide Conjugates.”American Chemical Society, pp.1543, 2014 https://centaur.reading.ac.uk/37092/
3. Janssen, J. A., Hofland, L. J., Strasburger, C. J., van den Dungen, E. S., & Thevis, M. (2016). The 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/
4. Peña JR, Pinney JR, Ayala P, Desai TA, Goldspink PH. Localized delivery of mechano-growth factor E-domain peptide via polymeric microstructures improves cardiac function following myocardial infarction. Biomaterials. 2015 Apr;46:26-34. doi: 10.1016/j.biomaterials.2014.12.050. Epub 2015 Jan 16. PMID: 25678113; PMCID: PMC4328136. https://pubmed.ncbi.nlm.nih.gov/25678113/
5. Doroudian G, Pinney J, Ayala P, Los T, Desai TA, Russell B. Sustained delivery of MGF peptide from micro rods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014 Oct;16(5):705-15. doi: 10.1007/s10544-014-9875-z. PMID: 24908137; PMCID: PMC4418932. https://pubmed.ncbi.nlm.nih.gov/24908137/
6. 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. doi: 10.3389/fphys.2019.00601. PMID: 31164836; PMCID: PMC6534059. https://pubmed.ncbi.nlm.nih.gov/31164836/
7. -T. Sun, K.-K. Cheung, S. W. N. Au, S. S. Yeung, and E. W. Yeung, “Overexpression of Mechano-Growth Factor Modulates Inflammatory Cytokine Expression and Macrophage Resolution in Skeletal Muscle Injury,” Front. Physiol., vol. 9, 2018. https://pmc.ncbi.nlm.nih.gov/articles/PMC6094977/
8. 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. PMID: 19567392. https://pubmed.ncbi.nlm.nih.gov/19567392/
9. Doroudian, J. Pinney, P. Ayala, T. Los, T. A. Desai, and B. Russell, “Sustained delivery of MGF peptide from micro rods attracts stem cells and reduces apoptosis of myocytes,” Biomed. Microdevices, vol. 16, no. 5, pp. 705–715, Oct. 2014. https://bjsm.bmj.com/content/39/11/787
10. 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. doi: 10.1007/s00264-010-1141-2. Epub 2010 Nov 6. PMID: 21057789; PMCID: PMC3167400. https://pubmed.ncbi.nlm.nih.gov/21057789/
11. Chen JT, Wang Y, Zhou ZF, Wei KW. [Mechano-growth factor regulated cyclic stretch-induced osteogenic differentiation and MMP-1, MMP-2 expression in human periodontal ligament cells by activating the MEK/ERK1/2 pathway]. Shanghai Kou Qiang Yi Xue. 2019 Feb;28(1):6-12. Chinese. PMID: 31080992. https://pubmed.ncbi.nlm.nih.gov/31080992/
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