Erythropoietin Alleviates Burn-induced Muscle Wasting.

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.

• Authors: Sheng-Hua Wu, I-Cheng Lu, Ming-Hong Tai, Chee-Yin Chai, Aij-Lie Kwan, Shu-Hung Huang
• Journal: International journal of medical sciences (Int J Med Sci) Vol. 17 Issue 1 Pg. 33-44 ( 2020) ISSN: 1449-1907 [Electronic] Australia
• PMID: 31929736 (Publication Type: Journal Article)
• Copyright: © The author(s).

Chemical References

• Muscle Proteins
• Smad2 Protein
• Smad2 protein, rat
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• erythropoietin, rat
• Erythropoietin
• Fbxo32 protein, rat
• SKP Cullin F-Box Protein Ligases
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Burns (drug therapy, genetics, metabolism, pathology)
• Caspase 3 (genetics)
• Connective Tissue (growth & development, metabolism)
• Disease Models, Animal
• Erythropoietin (genetics, pharmacology)
• Gene Expression Regulation (drug effects)
• Humans
• Muscle Proteins (genetics)
• Muscle Weakness (drug therapy, genetics, metabolism, pathology)
• Muscle, Skeletal (growth & development, metabolism, pathology)
• Muscular Atrophy (drug therapy, genetics, metabolism, pathology)
• Rats
• SKP Cullin F-Box Protein Ligases (genetics)
• Signal Transduction (drug effects)
• Smad2 Protein (genetics)
• Transforming Growth Factor beta1 (genetics)