The Effect of mechanical unloading on TRAF6 and MuRF1 genes expression in soleus muscle of male Wistar rats

Document Type : original article


1 Sport sciences, Faculty of Humanity and Litrutur, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran

2 Exercise physiology, Faculty of Humanity and Litrutur, Azad University of Kerman, Kerman, Iran

3 Sport sciences, Faculty of Humanity and Litrutur, Tarbiat Modares University, Tehran, Iran

4 Exercise physiology, Faculty of Humanity and Litrutur, Azad University of Kerman, Kerman, Iran.


Purpose: Because of exiting uncertainties in growth and maintenance of muscle mass processes, particular atrophy inducing inactivity, the aim of the present study was to investigate changes in the expression of atrogenic genes in the muscle of the rat in which the hind-limbs were kept under unloaded conditions.
Methods: For this purpose, 10 male Wistar rats were assign in two groups of suspension (n=5) and control (n=5) and the suspension group rats were kept for two weeks in this conditions. After 14 days, the soleus muscle was extracted and the expression of TRAf6 and MuRF1 genes was measured by real-time-Pcr method.
Results: The results of this study showed that after 14 days of hind-limb suspension, the relative weight of soleus muscle was significantly decreased (P=0.009). In addition, the expression of TRAF6 gene was significantly increased (P=0.033), but MuRF1 was not statistically significant (P=0.061).
Conclusion: Therefore, according to the results of this study, it can be stated that TRAF6 and its downstream factor, MuRF1, can be involved in the regulation of muscle mass in conditions of reduced muscular activity and mechanical unloading and as candidates for controlling muscle mass in conditions such as athlete's hospitalized after sports injuries or hind-limb unloading after injury to be considered.


[1] Fanzani A, Conraads VM, Penna F, Martinet W. Molecular and cellular mechanisms of skeletal muscle atrophy: an update. Journal of cachexia, sarcopenia and muscle. 2012;3(3):163-79.
[2] Verhees KJ, Schols AM, Kelders MC, Op den Kamp CM, van der Velden JL, Langen RC. Glycogen synthase kinase- 3β is required for the induction of skeletal muscle atrophy. American Journal of Physiology-Cell Physiology. 2011;301(5):C995-C1007.
[3] Baldwin KM, Haddad F, Pandorf CE, Roy RR, Edgerton VR. Alterations in muscle mass and contractile phenotype in response to unloading models: role of transcriptional /pretranslational mechanisms. Front Physiology. 2013 11;4:284.
[4] Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard J-C, Sassi AH, et al. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cellular and molecular life sciences. 2014;71(22):4361-71.
[5] Adams GR, Caiozzo VJ, Baldwin KM. Skeletal muscle unweighting: spaceflight and ground-based models. Journal of applied physiology. 2003;95(6):2185-201.
[6] Fitts RH, Riley DR, Widrick JJ. Physiology of a microgravity environment invited review: microgravity and skeletal muscle. Journal of applied physiology. 2000;89(2):823-39.
[7] Rennie MJ, Wackerhage H, Spangenburg EE, Booth FW. Control of the size of the human muscle mass. Annu Rev Physiol. 2004;66:799-828.
[8] Chopard A, Hillock S, Jasmin BJ. Molecular events and signalling pathways involved in skeletal muscle disuseā€induced atrophy and the impact of countermeasures. Journal of cellular and molecular medicine. 2009;13(9b):3032-50.
[9] Bialek P, Morris C, Parkington J, St. Andre M, Owens J, Yaworsky P, et al. Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy. Physiological genomics. 2011;43(19):1075-86.
[10] Paul PK, Gupta SK, Bhatnagar S, Panguluri SK, Darnay BG, Choi Y, et al. Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. The Journal of cell biology. 2010;191(7):1395-411.
[11] Tesch PA, von Walden F, Gustafsson T, Linnehan RM, Trappe TA. Skeletal muscle proteolysis in response to shortterm unloading in humans. Journal of applied physiology. 2008;105(3):902-6.
[12] Gustafsson T, Osterlund T, Flanagan JN, von Walden F, Trappe TA, Linnehan RM, et al. Effects of 3 days unloading on molecular regulators of muscle size in humans. Journal of applied physiology. 2010;109(3):721-7.
[13] Sun H, Gong Y, Qiu J, Chen Y, Ding F, Zhao Q. TRAF6 inhibition rescues dexamethasone-induced muscle atrophy. International journal of molecular sciences. 2014;15(6):11126-41.
[14] Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nature cell biology.
[15] Morey-Holton ER, Globus RK. Hindlimb unloading rodent model: technical aspects. Journal of applied physiology. 2002;92(4):1367-77.
[16] Al-Nassan S, Fujita N, Kondo H, Murakami S, Fujino H. Chronic exercise training down-regulates TNF-α and atrogin-1/MAFbx in mouse gastrocnemius muscle atrophy induced by hindlimb unloading. Acta histochemica et cytochemica. 2012;45(6):343-9.
[17] Labeit S, Kohl CH, Witt CC, Labeit D, Jung J, Granzier H. Modulation of muscle atrophy, fatigue and MLC phosphorylation
by MuRF1 as indicated by hindlimb suspension studies on MuRF1-KO mice. BioMed Research International.
[18] Polge C, Koulmann N, Claustre A, Jarzaguet M, Serrurier B, Combaret L, et al. UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension. The international journal of biochemistry & cell biology. 2016;79:488-93.
[19] Thoma A, Lightfoot AP. NF-kB and Inflammatory Cytokine Signalling: Role in Skeletal Muscle Atrophy. Adv Exp Med Biol. 2018;1088:267-279.
[20] Cornwell EW, Mirbod A, Wu CL, Kandarian SC, Jackman RW. C26 cancer-induced muscle wasting is IKKβ-dependent and NF-kappaB-independent. PLoS One. 2014; 29;9(1):e87776.
[21] Bilodeau PA, Coyne ES, Wing SS. The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation. American Journal of Physiology-Cell Physiology. 2016;311(3):C392-C403.
[22] Sato S, Ogura Y, Kumar A. TWEAK/Fn14 Signaling Axis Mediates Skeletal Muscle Atrophy and Metabolic Dysfunction Front Immunol. 2014 Jan 27;5:18.
[23] Tajrishi MM, Zheng TS, Burkly LC, Kumar A. The TWEAK-Fn14 pathway: a potent regulator of skeletal muscle biology in health and disease. Cytokine Growth Factor Rev. 2014 Apr;25(2):215-25.
[24] Walsh MC, Lee J, Choi Y. Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development,
function, and homeostasis of the immune system. Immunol Rev. 2015;266(1):72-92.
[25] Umasuthan N, Bathige SD, Revathy KS, Nam BH, Choi CY, Lee J. Molecular genomic- and transcriptional-aspects of a teleost TRAF6 homolog: Possible  nvolvement in immune responses of Oplegnathus fasciatus against pathogens. Fish Shellfish Immunol. 2015;42(1):66-78. 
  • Receive Date: 10 September 2018
  • Revise Date: 10 August 2019
  • Accept Date: 23 September 2019
  • First Publish Date: 19 February 2021
  • Publish Date: 19 February 2021