{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T19:20:36Z","timestamp":1782415236185,"version":"3.54.5"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T00:00:00Z","timestamp":1621641600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Intrahepatic cholangiocarcinoma (iCCA) is closely correlated with hepatic progenitor cell (HPC) expansion and liver fibrosis. Brahma\u2010related gene 1 (Brg1), an enzymatic subunit of the switch\/sucrose nonfermentable complex that is critical in stem cell maintenance and tumor promotion, is prominently up\u2010regulated in both HPCs and iCCA; however, its role in this correlation remains undefined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>A retrospective cohort study indicated that high Brg1 expression suggests poor prognosis in patients with iCCA. In chronically injured livers induced by a 0.1% 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine diet or bile duct ligation surgery, HPCs were dramatically activated, as indicated by their enhanced expression of Brg1 and a subset of stem cell markers; however, Brg1 ablation in HPCs strongly suppressed HPC expansion and liver fibrosis. Furthermore, in a chemically induced iCCA model, inhibition of Brg1 by a specific inhibitor or inducible gene ablation markedly improved histology and suppressed iCCA growth. Mechanistically, in addition to transcriptionally promoting both Wnt receptor genes and target genes, Brg1 was found to bind to the \u03b2\u2010catenin\/transcription factor 4 transcription complex, suggesting a possible approach for regulation of Wnt\/\u03b2\u2010catenin signaling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We have demonstrated the function of Brg1 in promoting HPC expansion, liver cirrhosis, and, ultimately, iCCA development in chronically injured livers, which is largely dependent on Wnt\/\u03b2\u2010catenin signaling. Our data suggest that therapies targeting Brg1\u2010expressing HPCs are promising for the treatment of liver cirrhosis and iCCA.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31780","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T03:11:44Z","timestamp":1614654704000},"page":"797-815","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":34,"title":["Brahma\u2010Related Gene 1 Inhibition Prevents Liver Fibrosis and Cholangiocarcinoma by Attenuating Progenitor Expansion"],"prefix":"10.1097","volume":"74","author":[{"given":"Yongjie","family":"Zhou","sequence":"first","affiliation":[{"name":"Laboratory of Pathology,Key Laboratory of Transplant Engineering and Immunology,NHC,West China Hospital,Sichuan University,Chengdu,China"},{"name":"Laboratory of Liver Transplantation,Frontiers Science Center for Disease\u2010Related Molecular Network,West China Hospital,Sichuan 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