Oncotarget

Research Papers:

Irisin treatment improves healing of dystrophic skeletal muscle

Musarrat Maisha Reza, Chu Ming Sim, Nathiya Subramaniyam, Xiaojia Ge, Mridula Sharma, Ravi Kambadur and Craig McFarlane _

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Oncotarget. 2017; 8:98553-98566. https://doi.org/10.18632/oncotarget.21636

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Abstract

Musarrat Maisha Reza1, Chu Ming Sim2, Nathiya Subramaniyam2, Xiaojia Ge2, Mridula Sharma3,4, Ravi Kambadur1,2,5 and Craig McFarlane2,6

1School of Biological Sciences, Nanyang Technological University, Singapore

2Singapore Institute for Clinical Sciences (A*STAR), Brenner Centre for Molecular Medicine, Singapore

3Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore

4Currently not affiliated with Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore

5Currently not affiliated with School of Biological Sciences, Nanyang Technological University, Singapore

6Current/Present address: Department of Molecular & Cell Biology, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, Australia

Correspondence to:

Craig McFarlane, email: [email protected]

Ravi Kambadur, email: [email protected]

Keywords: skeletal muscle; dystrophy; FNDC5; irisin; sarcolemmal stability

Received: May 16, 2017     Accepted: August 26, 2017     Published: October 06, 2017

ABSTRACT

Background: Irisin is an exercise induced myokine that is shown to promote browning of adipose tissue and hence, increase energy expenditure. Furthermore, our unpublished results indicate that Irisin improves myogenic differentiation and induces skeletal muscle hypertrophy. Since exercise induced skeletal muscle hypertrophy improves muscle strength, we wanted to investigate if ectopic injection of Irisin peptide improves skeletal muscle function in a mouse model of muscular dystrophy. This utility of Irisin peptide is yet to be studied in animal models.

Methods: In order to test this hypothesis, we expressed and purified recombinant murine Irisin peptide from E. coli. Three- to six-week-old male mdx mice were injected IP with either vehicle (dialysis buffer) or Irisin recombinant peptide for two or four weeks, three times-a-week.

Results: Irisin injection increased muscle weights and enhanced grip strength in mdx mice. Improved muscle strength can be attributed to the significant hypertrophy observed in the Irisin injected mdx mice. Moreover, Irisin treatment resulted in reduced accumulation of fibrotic tissue and myofiber necrosis in mdx mice. In addition, Irisin improved sarcolemmal stability, which is severely compromised in mdx mice.

Conclusion: Irisin injection induced skeletal muscle hypertrophy, improved muscle strength and reduced necrosis and fibrotic tissue in a murine dystrophy model. These results demonstrate the potential therapeutic value of Irisin in muscular dystrophy.


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