{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:27:02Z","timestamp":1792787222759,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T00:00:00Z","timestamp":1545955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003693","name":"Korea Institute of Science and Technology","doi-asserted-by":"publisher","award":["2Z05310"],"award-info":[{"award-number":["2Z05310"]}],"id":[{"id":"10.13039\/501100003693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008122","name":"Iran Telecommunication Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008122","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2018M3A9C8020027"],"award-info":[{"award-number":["NRF-2018M3A9C8020027"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2017R1A2B3005015"],"award-info":[{"award-number":["NRF-2017R1A2B3005015"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fibrosis is characterized by the increased accumulation of extracellular matrix (ECM), which drives abnormal cell proliferation and progressive organ dysfunction in many inflammatory and metabolic diseases. Studies have shown that halofuginone, a racemic halogenated derivative, inhibits glutamyl\u2010prolyl\u2010transfer RNA\u2010synthetase (EPRS)\u2010mediated fibrosis. However, the mechanism by which this occurs is unclear. We explored the mechanistic aspects of how EPRS could develop liver fibrotic phenotypes in cells and animal models. Treatment with TGF\u2010\u03b21 up\u2010regulated fibronectin and collagen I levels in LX2 hepatic stellate cells. This effect was inhibited in prolyl\u2010transfer RNA synthetase (PRS)\u2010suppressed LX2 cells. Using the promoter luciferase assay, TGF\u2010\u03b21\u2013mediated collagen I, \u03b11 chain transcription and \u03b32 basal laminin transcription in LX2 cells were down\u2010regulated by EPRS suppression, suggesting that EPRS may play roles in ECM production at transcriptional levels. Furthermore, signal transducer and activator of transcription (STAT) signaling activation was involved in the effects of TGF\u2010\u03b21 on ECM expression in a PRS\u2010dependent manner. This was mediated\n                    <jats:italic>via<\/jats:italic>\n                    a protein\u2010protein complex formation consisting of TGF\u2010\u03b21 receptor, EPRS, Janus kinases, and STAT6. Additionally, ECM expression in fibrotic livers overlapped with EPRS expression along fibrotic septa regions and was positively correlated with STAT6 activation in carbon tetrachloride\u2010treated mice. This was less obvious in livers of\n                    <jats:italic>Eprs<\/jats:italic>\n                    <jats:sup>\u2212\/+<\/jats:sup>\n                    mice. These findings suggest that, during fibrosis development, EPRS plays roles in nontranslational processes of ECM expression\n                    <jats:italic>via<\/jats:italic>\n                    intracellular signaling regulation upon TGF\u2010\u03b21 stimulation.\u2014Song, D.\u2010G., Kim, D., Jung, J. W., Nam, S. H., Kim, J. E., Kim, H.\u2010J., Kim, J. H., Lee, S.\u2010J., Pan, C.\u2010H., Kim, S., Lee, J. W. Glutamyl\u2010prolyl\u2010tRNA synthetase induces fibrotic extracellular matrix\n                    <jats:italic>via<\/jats:italic>\n                    both transcriptional and translational mechanisms. FASEB J. 33, 4341\u20134354 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801344rr","type":"journal-article","created":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T13:08:36Z","timestamp":1546002516000},"page":"4341-4354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Glutamyl\u2010prolyl\u2010tRNA synthetase induces fibrotic extracellular matrix\n                    <i>via<\/i>\n                    both transcriptional and translational mechanisms"],"prefix":"10.1096","volume":"33","author":[{"given":"Dae-Geun","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pharmacy Research Institute of Pharmaceutical Sciences College of Pharmacy Seoul National University  Seoul Republic of Korea"},{"name":"Systems 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