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Int J Med Sci 2020; 17(1):33-44. doi:10.7150/ijms.38590 This issue Cite

Research Paper

Erythropoietin Alleviates Burn-induced Muscle Wasting

Sheng-Hua Wu^1,2,3,4, I-Cheng Lu^1,2,3, Ming-Hong Tai^5,6, Chee-Yin Chai^7,8,9, Aij-Lie Kwan^8,10, Shu-Hung Huang^10,11,12✉

1. Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
2. Department of Anesthesiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
3. Department of Anesthesiology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
4. Department of Anesthesiology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
5. Center for Neuroscience, National Sun Yat-Sen University, Kaohsiung, Taiwan.
6. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
7. Departments of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
8. Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
9. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
10. Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
11. Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
12. Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

✉ Corresponding author: Shu-Hung Huang, Tel: 886-7-3121101*7676; E-mail: huangsh63com

Abstract

Background: Burn injury induces long-term skeletal muscle pathology. We hypothesized EPO could attenuate burn-induced muscle fiber atrophy.

Methods: Rats were allocated into four groups: a sham burn group, an untreated burn group subjected to third degree hind paw burn, and two burn groups treated with weekly or daily EPO for four weeks. Gastrocnemius muscle was analyzed at four weeks post-burn.

Results: EPO attenuated the reduction of mean myofiber cross-sectional area post-burn and the level of the protective effect was no significant difference between two EPO-treated groups (p=0.784). Furthermore, EPO decreased the expression of atrophy-related ubiquitin ligase, atrogin-1, which was up-regulated in response to burn. Compared to untreated burn rats, those receiving weekly or daily EPO groups had less cell apoptosis by TUNEL assay. EPO decreased the expression of cleaved caspase 3 (key factor in the caspase-dependent pathway) and apoptosis-inducing factor (implicated in the caspase-independent pathway) after burn. Furthermore, EPO alleviated connective tissue overproduction following burn via transforming growth factor beta 1-Smad2/3 pathway. Daily EPO group caused significant erythrocytosis compared with untreated burn group but not weekly EPO group.

Conclusion: EPO therapy attenuated skeletal muscle apoptosis and fibrosis at four weeks post-burn. Weekly EPO may be a safe and effective option in muscle wasting post-burn.

Keywords: Erythropoietin, Muscle fiber atrophy, Burn injury, Apoptosis Inducing Factor, Transforming Growth Factor beta1

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