The role of proteasome in muscle wasting of experimental arthritis
Abstract Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treat...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Advances in Rheumatology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s42358-023-00292-5 |
| _version_ | 1797863235035070464 |
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| author | Vivian Oliveira Nunes Teixeira Bárbara Jonson Bartikoski Rafaela Cavalheiro do Espirito Santo Paulo Vinícius Gil Alabarse Khetam Ghannan Jordana Miranda Souza Silva Lidiane Isabel Filippin Fernanda Visioli Lorena Martinez-Gamboa Eugen Feist Ricardo Machado Xavier |
| author_facet | Vivian Oliveira Nunes Teixeira Bárbara Jonson Bartikoski Rafaela Cavalheiro do Espirito Santo Paulo Vinícius Gil Alabarse Khetam Ghannan Jordana Miranda Souza Silva Lidiane Isabel Filippin Fernanda Visioli Lorena Martinez-Gamboa Eugen Feist Ricardo Machado Xavier |
| author_sort | Vivian Oliveira Nunes Teixeira |
| collection | DOAJ |
| description | Abstract Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. Methods Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMβ5, PMSβ6, PSMβ7, PSMβ8, PSMβ9, and PSMβ10), and protein (PSMβ1, PSMβ5, PSMβ1i, PSMβ5i) expression of proteasome subunits. Results Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMβ8 and PSMβ9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSβ6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMβ5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMβ5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit β1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). Conclusions The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMβ8 and PSMβ9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting. |
| first_indexed | 2024-04-09T22:32:18Z |
| format | Article |
| id | doaj.art-eb8e31c54a134de4a87ffe6ab567c7f9 |
| institution | Directory Open Access Journal |
| issn | 2523-3106 |
| language | English |
| last_indexed | 2024-04-09T22:32:18Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Advances in Rheumatology |
| spelling | doaj.art-eb8e31c54a134de4a87ffe6ab567c7f92023-03-22T12:42:58ZengBMCAdvances in Rheumatology2523-31062023-03-0163111210.1186/s42358-023-00292-5The role of proteasome in muscle wasting of experimental arthritisVivian Oliveira Nunes Teixeira0Bárbara Jonson Bartikoski1Rafaela Cavalheiro do Espirito Santo2Paulo Vinícius Gil Alabarse3Khetam Ghannan4Jordana Miranda Souza Silva5Lidiane Isabel Filippin6Fernanda Visioli7Lorena Martinez-Gamboa8Eugen Feist9Ricardo Machado Xavier10Medical Sciences Program, Medicine Department, Universidade Federal do Rio Grande do SulMedical Sciences Program, Medicine Department, Universidade Federal do Rio Grande do SulMedical Sciences Program, Medicine Department, Universidade Federal do Rio Grande do SulMedical Sciences Program, Medicine Department, Universidade Federal do Rio Grande do SulSchwerpunkt Rheumatologie und Klinische Immunologie, Charité-Universitätsmedizin BerlinMedical Sciences Program, Medicine Department, Universidade Federal do Rio Grande do SulLaboratório de Doenças Autoimunes, Hospital de Clínicas de Porto AlegrePatology Department, Faculdade de Odontologia, Universidade Federal do Rio Grande do SulSchwerpunkt Rheumatologie und Klinische Immunologie, Charité-Universitätsmedizin BerlinSchwerpunkt Rheumatologie und Klinische Immunologie, Charité-Universitätsmedizin BerlinMedical Sciences Program, Medicine Department, Universidade Federal do Rio Grande do SulAbstract Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. Methods Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMβ5, PMSβ6, PSMβ7, PSMβ8, PSMβ9, and PSMβ10), and protein (PSMβ1, PSMβ5, PSMβ1i, PSMβ5i) expression of proteasome subunits. Results Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMβ8 and PSMβ9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSβ6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMβ5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMβ5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit β1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). Conclusions The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMβ8 and PSMβ9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting.https://doi.org/10.1186/s42358-023-00292-5Experimental arthritisMuscle wastingProteasomeTNF inhibitor |
| spellingShingle | Vivian Oliveira Nunes Teixeira Bárbara Jonson Bartikoski Rafaela Cavalheiro do Espirito Santo Paulo Vinícius Gil Alabarse Khetam Ghannan Jordana Miranda Souza Silva Lidiane Isabel Filippin Fernanda Visioli Lorena Martinez-Gamboa Eugen Feist Ricardo Machado Xavier The role of proteasome in muscle wasting of experimental arthritis Advances in Rheumatology Experimental arthritis Muscle wasting Proteasome TNF inhibitor |
| title | The role of proteasome in muscle wasting of experimental arthritis |
| title_full | The role of proteasome in muscle wasting of experimental arthritis |
| title_fullStr | The role of proteasome in muscle wasting of experimental arthritis |
| title_full_unstemmed | The role of proteasome in muscle wasting of experimental arthritis |
| title_short | The role of proteasome in muscle wasting of experimental arthritis |
| title_sort | role of proteasome in muscle wasting of experimental arthritis |
| topic | Experimental arthritis Muscle wasting Proteasome TNF inhibitor |
| url | https://doi.org/10.1186/s42358-023-00292-5 |
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