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In this study, we aimed to investigate the potential role of the immunoproteasome subunit \u03b25i and retinoic acid-inducible gene-I (RIG-I) in DM-associated muscle atrophy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The expression of \u03b25i and RIG-I in the muscles of 16 patients with DM was examined by PCR, western blotting and immunohistochemistry. The associations between \u03b25i and RIG-I expression levels and muscle disease severity were evaluated. Lentivirus transduction was used to overexpress \u03b25i in human skeletal muscle myoblasts (HSMMs) and consequent cell functional changes were studied in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\u03b25i and RIG-I expression in the muscle of patients with DM was significantly increased and closely associated with muscle disease severity. Immunohistochemistry and immunofluorescence analyses showed the marked colocalised expression of \u03b25i and RIG-I in perifascicular myofibres. \u03b25i overexpression in HSMMs significantly upregulated RIG-I, the muscle atrophy marker MuRF1, type I IFN-related proteins (MxA and IFN\u03b2) and NF-\u03baB pathway-related proteins (pI\u03baB\u03b1, pIRF3 and pNF-\u03baBp65). In addition, the viability of HSMMs decreased significantly after \u03b25i overexpression and was partly recovered by treatment with a \u03b25i inhibitor (PR957). Moreover, activation of RIG-I by pppRNA upregulated IFN\u03b2 and MuRF1 and reduced the cell viability of HSMMs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The immunoproteasome subunit \u03b25i promotes perifascicular muscle atrophy in DM via RIG-I upregulation; our findings suggest a pathomechanistic role of \u03b25i and RIG-I in DM-associated muscle damage, highlighting these components as potential therapeutic targets for the treatment of DM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2022-002818","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T11:00:20Z","timestamp":1677582020000},"page":"e002818","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Immunoproteasome subunit \u03b25i promotes perifascicular muscle atrophy in dermatomyositis by 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