{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:02:22Z","timestamp":1790650942758,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK111866,R56DK088837,DK099205,AA028550,DK101737,AA011999,DK120515,AA029019,DK091183,P42ES010337,R44DK115242,R01CA285997"],"award-info":[{"award-number":["R01DK111866,R56DK088837,DK099205,AA028550,DK101737,AA011999,DK120515,AA029019,DK091183,P42ES010337,R44DK115242,R01CA285997"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sanford Stem Cell Institute UC San Diego","award":["Sanford Stem Cell Fitness"],"award-info":[{"award-number":["Sanford Stem Cell Fitness"]}]},{"name":"Sanford Stem Cell Institute UC San Diego","award":["Space Medicine Center"],"award-info":[{"award-number":["Space Medicine Center"]}]},{"DOI":"10.13039\/501100002631","name":"Gachon University","doi-asserted-by":"crossref","award":["GCU-202500490001"],"award-info":[{"award-number":["GCU-202500490001"]}],"id":[{"id":"10.13039\/501100002631","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2025-25431473,RS-2025-16067292,RS-2025-16067036"],"award-info":[{"award-number":["RS-2025-25431473,RS-2025-16067292,RS-2025-16067036"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,22]]},"abstract":"<jats:p>\n                    Chronic liver injury results in activation of quiescent hepatic stellate cells (HSCs) into collagen type I\u2013producing activated HSCs that make the liver fibrotic. We identified ETS1 and ETS2 (ETS1\/2) as lineage-specific transcription factors regulating HSC phenotypes. Here, we investigated the role of ETS1\/2 in HSCs in liver fibrosis using toxic liver injury models and 3D human liver spheroids. Liver fibrosis was induced in WT and HSC-specific Ets1-KO (\n                    <jats:italic>Ets1<\/jats:italic>\n                    <jats:sup>\u0394HSC<\/jats:sup>\n                    ) and Ets2-KO (\n                    <jats:italic>Ets2<\/jats:italic>\n                    <jats:sup>\u0394HSC<\/jats:sup>\n                    ) mice by administration of CCl\n                    <jats:sub>4<\/jats:sub>\n                    for 6 weeks, followed by cessation of liver injury for 2 weeks. Liver fibrosis was more severe in\n                    <jats:italic>Ets1<\/jats:italic>\n                    <jats:sup>\u0394HSC<\/jats:sup>\n                    and to a lesser extent\n                    <jats:italic>Ets2<\/jats:italic>\n                    <jats:sup>\u0394HSC<\/jats:sup>\n                    mice compared with WT mice. Regression of liver fibrosis was suppressed only in\n                    <jats:italic>Ets1<\/jats:italic>\n                    <jats:sup>\u0394HSC<\/jats:sup>\n                    mice, indicating Ets1 is the predominant isoform maintaining a quiescent-like phenotype in HSCs. Similar results were obtained in a metabolic dysfunction\u2013associated steatohepatitis (MASH) model using 3D human liver spheroids. Knockdown of ETS1 in human HSCs caused upregulation of fibrogenic genes in MASH human liver spheroids and prevented fibrosis regression. ETS1 regulated the quiescent HSC phenotype via the CREB-regulated transcription coactivator 2 (CRTC2)\/PGC1\u03b1\/PPAR\u03b3 pathway. Knockdown of CRTC2 abrogated PPAR\u03b3 responses and facilitated HSC activation. These findings suggest that ETS1 may represent a therapeutic target for antifibrotic therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.195242","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T17:01:19Z","timestamp":1762275679000},"source":"Crossref","is-referenced-by-count":7,"title":["ETS1 suppresses hepatic stellate cell activation and liver fibrosis"],"prefix":"10.1172","volume":"10","author":[{"given":"Wonseok","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Surgery, University of California San Diego School of Medicine, La Jolla, California, USA."},{"name":"College of Pharmacy, Gachon University, Incheon, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Surgery, University of California San Diego School of Medicine, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Brin","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Miciano","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, and"},{"name":"Center for Epigenomics, University of California San Diego School of Medicine, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadatsugu","family":"Sakane","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Surgery, University of California San Diego School of Medicine, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanani","family":"Hokutan","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Department 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