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Volume 23
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10.3390/ijms23084222
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Article

MIF1 and MIF2 Myostatin Peptide Inhibitors as Potent Muscle Mass Regulators

by
Eun Ju Lee
1,2,†,
Sibhghatulla Shaikh
1,2,†,
Mohammad Hassan Baig
3,
So-Young Park
4,
Jeong Ho Lim
1,2,
Syed Sayeed Ahmad
1,2,
Shahid Ali
1,2,
Khurshid Ahmad
1,2,* and
Inho Choi
1,2,*
1
Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea
2
Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Korea
3
Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea
4
Department of Physiology, College of Medicine, Yeungnam University, Daegu 42415, Korea
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(8), 4222; https://doi.org/10.3390/ijms23084222
Submission received: 14 March 2022 / Revised: 8 April 2022 / Accepted: 8 April 2022 / Published: 11 April 2022
(This article belongs to the Section Molecular Biology)
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Abstract

The use of peptides as drugs has progressed over time and continues to evolve as treatment paradigms change and new drugs are developed. Myostatin (MSTN) inhibition therapy has shown great promise for the treatment of muscle wasting diseases. Here, we report the MSTN-derived novel peptides MIF1 (10-mer) and MIF2 (10-mer) not only enhance myogenesis by inhibiting MSTN and inducing myogenic-related markers but also reduce adipogenic proliferation and differentiation by suppressing the expression of adipogenic markers. MIF1 and MIF2 were designed based on in silico interaction studies between MSTN and its receptor, activin type IIB receptor (ACVRIIB), and fibromodulin (FMOD). Of the different modifications of MIF1 and MIF2 examined, Ac-MIF1 and Ac-MIF2-NH2 significantly enhanced cell proliferation and differentiation as compared with non-modified peptides. Mice pretreated with Ac-MIF1 or Ac-MIF2-NH2 prior to cardiotoxin-induced muscle injury showed more muscle regeneration than non-pretreated controls, which was attributed to the induction of myogenic genes and reduced MSTN expression. These findings imply that Ac-MIF1 and Ac-MIF2-NH2 might be valuable therapeutic agents for the treatment of muscle-related diseases.
Keywords: skeletal muscle; peptides; myostatin; myogenesis; muscle regeneration skeletal muscle; peptides; myostatin; myogenesis; muscle regeneration
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MDPI and ACS Style

Lee, E.J.; Shaikh, S.; Baig, M.H.; Park, S.-Y.; Lim, J.H.; Ahmad, S.S.; Ali, S.; Ahmad, K.; Choi, I. MIF1 and MIF2 Myostatin Peptide Inhibitors as Potent Muscle Mass Regulators. Int. J. Mol. Sci. 2022, 23, 4222. https://doi.org/10.3390/ijms23084222

AMA Style

Lee EJ, Shaikh S, Baig MH, Park S-Y, Lim JH, Ahmad SS, Ali S, Ahmad K, Choi I. MIF1 and MIF2 Myostatin Peptide Inhibitors as Potent Muscle Mass Regulators. International Journal of Molecular Sciences. 2022; 23(8):4222. https://doi.org/10.3390/ijms23084222

Chicago/Turabian Style

Lee, Eun Ju, Sibhghatulla Shaikh, Mohammad Hassan Baig, So-Young Park, Jeong Ho Lim, Syed Sayeed Ahmad, Shahid Ali, Khurshid Ahmad, and Inho Choi. 2022. "MIF1 and MIF2 Myostatin Peptide Inhibitors as Potent Muscle Mass Regulators" International Journal of Molecular Sciences 23, no. 8: 4222. https://doi.org/10.3390/ijms23084222

APA Style

Lee, E. J., Shaikh, S., Baig, M. H., Park, S.-Y., Lim, J. H., Ahmad, S. S., Ali, S., Ahmad, K., & Choi, I. (2022). MIF1 and MIF2 Myostatin Peptide Inhibitors as Potent Muscle Mass Regulators. International Journal of Molecular Sciences, 23(8), 4222. https://doi.org/10.3390/ijms23084222

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