{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:57:08Z","timestamp":1791982628788,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Hepatic stellate cells (HSCs), a key player in the progression of liver fibrosis, are activated by various inflammatory stimuli and converted to myofibroblast\u2010like cells with excessive collagen production. Despite many attempts to suppress activation of HSCs or inhibit collagen production in activated HSCs, their clinical applications have not been established yet. Recently, the deactivation of HSCs has been reported as a mechanism underlying the reversibility of experimental liver fibrosis. In the present study, we sought for deactivation factors of HSCs that induce regression of established liver fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      We identified transcription factor 21 (Tcf21) as one of the transcription factors whose expression was up\u2010regulated in parallel to the differentiation of fetal HSCs. Expression of Tcf21 in HSCs remarkably decreased during culture\u2010induced activation\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and in murine and human fibrotic liver tissue\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . This reduced Tcf21 expression was recovered during the spontaneous regression of murine liver fibrosis. Tcf21 was also examined for its effects by adeno\u2010associated virus serotype 6\u2010mediated\n                      <jats:italic toggle=\"yes\">Tcf21<\/jats:italic>\n                      gene transfer into cultured activated HSCs and mice with carbon tetrachloride\u2010 or methionine\u2010choline deficient diet\u2010induced liver fibrosis. Overexpression of Tcf21 in activated HSCs not only suppressed fibrogenic gene expression but also restored cells, at least in part, to a quiescent phenotype both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . These phenotypic changes of HSCs were accompanied by the regression of steatohepatitis and fibrosis and improved hepatic architecture and function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tcf21 has been identified as a deactivation factor of fibrogenic HSCs, providing insight into a treatment strategy for the otherwise intractable liver fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.30965","type":"journal-article","created":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T03:00:36Z","timestamp":1569294036000},"page":"1437-1452","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":87,"title":["A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice"],"prefix":"10.1097","volume":"71","author":[{"given":"Yasuhiro","family":"Nakano","sequence":"first","affiliation":[{"name":"Center for Matrix Biology and Medicine,Graduate School of Medicine,Tokai University,Isehara,Japan"},{"name":"Department of Innovative Medical Science,Tokai University School of Medicine,Isehara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihide","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Center for Matrix Biology and Medicine,Graduate School of Medicine,Tokai University,Isehara,Japan"},{"name":"Department of Molecular Life Sciences,Tokai University School of Medicine,Isehara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Sumiyoshi","sequence":"additional","affiliation":[{"name":"Center for Matrix Biology and Medicine,Graduate School of Medicine,Tokai University,Isehara,Japan"},{"name":"Department of Innovative Medical Science,Tokai University School of Medicine,Isehara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Tsuruya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Internal Medicine,Tokai University School of Medicine,Isehara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatehiro","family":"Kagawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Internal Medicine,Tokai University School of Medicine,Isehara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Center for Matrix Biology and Medicine,Graduate School of Medicine,Tokai University,Isehara,Japan"},{"name":"Department of Innovative Medical Science,Tokai University School of Medicine,Isehara,Japan"},{"name":"Institute of Medical Sciences,Tokai University,Isehara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,3,6]]},"reference":[{"key":"hep30965-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1172\/JCI93563","article-title":"Resolution of organ fibrosis","volume":"128","year":"2018","journal-title":"J Clin Invest"},{"key":"hep30965-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1172\/JCI66369","article-title":"Hepatic stellate cells in liver development, regeneration, and cancer","volume":"123","year":"2013","journal-title":"J Clin Invest"},{"key":"hep30965-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1006\/bbrc.1998.9345","article-title":"Activation of Proalpha 2(I) collagen promoter during hepatic fibrogenesis in transgenic mice","volume":"250","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"hep30965-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jhep.2015.01.036","article-title":"\u03b2\u2010PDGF receptor expressed by hepatic stellate cells regulates fibrosis in murine liver injury, but not carcinogenesis","volume":"63","year":"2015","journal-title":"J Hepatol"},{"key":"hep30965-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep30965-bib-0006-20241017","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1172\/JCI1018","article-title":"Mechanisms of spontaneous resolution of rat liver fibrosis. 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