{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:55:54Z","timestamp":1790222154113,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T00:00:00Z","timestamp":1502928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T00:00:00Z","timestamp":1502928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dermatomyositis is an inflammatory myopathy characterized by symmetrical proximal muscle weakness and skin changes. Muscle biopsy hallmarks include perifascicular atrophy, loss of intramuscular capillaries, perivascular and perimysial inflammation and the overexpression of IFN-inducible genes. Among them, the retinoic-acid inducible gene 1 (RIG-I) is specifically overexpressed in perifascicular areas of dermatomyositis muscle. The aim of this work was to study if RIG-I expression may be modulated by hypoxia using an <jats:italic>in vitro<\/jats:italic> approach. We identified putative hypoxia response elements (HRE) in <jats:italic>RIG-I<\/jats:italic> regulatory regions and luciferase assays confirmed that <jats:italic>RIG-I<\/jats:italic> is a new HIF-inducible gene. We observed an increase expression of RIG-I both by Real time PCR and Western blot in hypoxic conditions in human muscle cells. Cell transfection with a constitutive RIG-I expression vector increased levels of phospho-IRF-3, indicating that RIG-I promotes binding of transcription factors to the enhancer sequence of IFN. Moreover, release of IFN-\u03b2 was observed in hypoxic conditions. Finally, HIF-1\u03b1 overexpression was confirmed in the muscle biopsies and in some RIG-I positive perifascicular muscle fibres but not in controls. Our results indicate that hypoxia triggers the production of IFN-I <jats:italic>in vitro<\/jats:italic>, and may contribute to the pathogenesis of DM together with other inflammatory factors.<\/jats:p>","DOI":"10.1038\/s41598-017-09309-8","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T11:54:30Z","timestamp":1502452470000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Hypoxia triggers IFN-I production in muscle: Implications in dermatomyositis"],"prefix":"10.1038","volume":"7","author":[{"given":"Noem\u00ed","family":"De Luna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Su\u00e1rez-Calvet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinta","family":"Lleix\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Diaz-Manera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Oliv\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Illa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3942-3436","authenticated-orcid":false,"given":"Eduard","family":"Gallardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,17]]},"reference":[{"key":"9309_CR1","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1056\/NEJMra1402225","volume":"372","author":"MC Dalakas","year":"2015","unstructured":"Dalakas, M. C. Inflammatory muscle diseases. N Engl J Med \n                           372, 1734\u20131747 (2015).","journal-title":"N Engl J Med"},{"key":"9309_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/1740-2557-3-2","volume":"3","author":"K Nagaraju","year":"2006","unstructured":"Nagaraju, K. et al. Endothelial cell activation and neovascularization are prominent in dermatomyositis. J Autoimmune Dis \n                           3, 2 (2006).","journal-title":"J Autoimmune Dis"},{"key":"9309_CR3","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1136\/annrheumdis-2012-201822","volume":"72","author":"C Gitiaux","year":"2013","unstructured":"Gitiaux, C. et al. Whole microvascular unit deletions in dermatomyositis. 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