In 1996, Goldspink and colleagues identified the expression of the mRNA of an insulin-like growth factor 1 (IGF-1) isoform in response to mechanical stress. Consequently, substantial research into the so-called mechano growth factor (MGF) and its modus operandi followed until today. Promising preclinical results were obtained by using the synthetic, 24-amino acid residues spanning peptide translated from the exons 4–6 of IGF-1Ec (which was later referred to as the mechano growth factor MGF peptide), particularly with regard to increased muscle myoblast proliferation. In both animal and human skeletal muscle three transcripts encoding for these splice variants (IGF‐IEa, IGF‐IEb and IGF‐IEc, also known as MGF) can be identified.
The IGF-1 gene consists of six exons, and alternative splicing has led to the identification of two different mRNA transcripts in rodents, IGF-1Ea and mechano-growth factor (MGF). IGF-1Ea is the main isoform produced by the liver under the control of growth hormone (GH), and MGF was initially detected in skeletal muscle and was shown to be significantly upregulated by mechanical stimulation. The MGF splice variant differs from IGF-1Ea by a 52-bp insert within the E domain of exon 5. This insert results in a translational frame shift that leads to a carboxy terminal sequence different from that of IGF-1Ea. Thus, two IGF-1 precursor polypeptides are raised from the different IGF-1 transcripts. These IGF-1 propeptides yield the same mature IGF-1 peptide, which is derived from the highly conserved exons 3 and 4 of the IGF-1 gene. These exons are known to code for the binding domain of the IGF-1 receptor (IGF-1R).
Insulinlike growth factor-1 (IGF-1) expression is implicated in myocardial pathophysiology, and two IGF-1 mRNA splice variants have been detected in rodents, IGF-1Ea and mechano-growth factor (MGF). Research fellow investigated the expression pattern of IGF-1 gene transcripts in rat myocardium from 1 h up to 8 wks after myocardial infarction induced by left anterior descending coronary artery ligation. In addition, they characterized IGF-1 and MGF E peptide action and their respective signaling in H9C2 myocardial-like cells in vitro. IGF-1Ea and MGF expression were significantly increased, both at transcriptional and translational levels, during the late postinfarction period (4 and 8 wks) in infarcted rat myocardium. Measurements of serum IGF-1 levels in infarcted rats were initially decreased (24h up to 1wk) but remained unaltered throughout the late experimental phase (4 to 8 wks) compared with sham-operated rats. Furthermore, specific anti–IGF-1R neutralizing antibody failed to block the synthetic MGF E peptide action, whereas it completely blocked IGF-1 action on the proliferation of H9C2 cells. Moreover, this synthetic MGF E peptide did not activate Akt phosphorylation, whereas it activated ERK1/2 in H9C2 rat myocardial cells. These data support the role of IGF-1 expression in the myocardial repair process and suggest that synthetic MGF E peptide actions may be mediated via an IGF-1R independent pathway in rat myocardial cells, as suggested by the study team in vitro experiments. All of the data suggest that in rat myocardium, IGF-1 transcript expression is upregulated during the late postinfarction period, whereas in rat myocardial cells in vitro, MGF E peptide exerts autonomous, IGF-1R–independent action.
MGF (Mechano Growth Factor) Peptide
MGF (Mechano Growth Factor) Peptide
Synonyms: Mechano Growth Factor, IGF-1 Ec
Chemical Sequence: Tyr-Gln-Pro-Pro-Ser-Thr-Asn-Lys-Asn-Thr-Lys-Ser-Gln-Arg-Arg-Lys-Gly-Ser-Thr-Phe-Glu-Glu-Arg-Lys
Molecular formula: C121H200N42O39
Molar Mass: 2867.14
In 1996, Goldspink and colleagues identified the expression of the mRNA of an insulin-like growth factor 1 (IGF-1) isoform in response to mechanical stress. Consequently, substantial research into the so-called mechano growth factor (MGF) and its modus operandi followed until today. Promising preclinical results were obtained by using the synthetic, 24-amino acid residues spanning peptide translated from the exons 4–6 of IGF-1Ec (which was later referred to as the mechano growth factor MGF peptide), particularly with regard to increased muscle myoblast proliferation. In both animal and human skeletal muscle three transcripts encoding for these splice variants (IGF‐IEa, IGF‐IEb and IGF‐IEc, also known as MGF) can be identified.
The IGF-1 gene consists of six exons, and alternative splicing has led to the identification of two different mRNA transcripts in rodents, IGF-1Ea and mechano-growth factor (MGF). IGF-1Ea is the main isoform produced by the liver under the control of growth hormone (GH), and MGF was initially detected in skeletal muscle and was shown to be significantly upregulated by mechanical stimulation. The MGF splice variant differs from IGF-1Ea by a 52-bp insert within the E domain of exon 5. This insert results in a translational frame shift that leads to a carboxy terminal sequence different from that of IGF-1Ea. Thus, two IGF-1 precursor polypeptides are raised from the different IGF-1 transcripts. These IGF-1 propeptides yield the same mature IGF-1 peptide, which is derived from the highly conserved exons 3 and 4 of the IGF-1 gene. These exons are known to code for the binding domain of the IGF-1 receptor (IGF-1R).
Insulinlike growth factor-1 (IGF-1) expression is implicated in myocardial pathophysiology, and two IGF-1 mRNA splice variants have been detected in rodents, IGF-1Ea and mechano-growth factor (MGF). Research fellow investigated the expression pattern of IGF-1 gene transcripts in rat myocardium from 1 h up to 8 wks after myocardial infarction induced by left anterior descending coronary artery ligation. In addition, they characterized IGF-1 and MGF E peptide action and their respective signaling in H9C2 myocardial-like cells in vitro. IGF-1Ea and MGF expression were significantly increased, both at transcriptional and translational levels, during the late postinfarction period (4 and 8 wks) in infarcted rat myocardium. Measurements of serum IGF-1 levels in infarcted rats were initially decreased (24h up to 1wk) but remained unaltered throughout the late experimental phase (4 to 8 wks) compared with sham-operated rats. Furthermore, specific anti–IGF-1R neutralizing antibody failed to block the synthetic MGF E peptide action, whereas it completely blocked IGF-1 action on the proliferation of H9C2 cells. Moreover, this synthetic MGF E peptide did not activate Akt phosphorylation, whereas it activated ERK1/2 in H9C2 rat myocardial cells. These data support the role of IGF-1 expression in the myocardial repair process and suggest that synthetic MGF E peptide actions may be mediated via an IGF-1R independent pathway in rat myocardial cells, as suggested by the study team in vitro experiments. All of the data suggest that in rat myocardium, IGF-1 transcript expression is upregulated during the late postinfarction period, whereas in rat myocardial cells in vitro, MGF E peptide exerts autonomous, IGF-1R–independent action.
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