{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:54:15Z","timestamp":1792004055456,"version":"4.4.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>In chronic hepatic diseases where treatment strategies are not available, deposited fibrotic tissues deteriorate the intrinsic regeneration capacity of the liver by creating special restrictions. Thus, if the anti\u2010fibrosis modality is efficiently applied, the regeneration capacity of the liver should be reactivated even in such refractory hepatic diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rat liver fibrosis was induced by dimethyl\u2010nitrosamine (DMN). Another liver fibrosis model was established in CCl4 treated Sox9CreERT2ROSA26: YFP mice. To resolve hepatic fibrosis, vitamin A\u2010coupled liposomes containing siRNA HSP47 (VA\u2010liposome siHSP47) were employed. EpCAM\u00a0+\u00a0hepatic progenitor cells from GFP rats were transplanted to DMN rat liver to examine their trans\u2010differentiation into hepatic cells after resolution of liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Even under continuous exposure to such strong hepatotoxin as DMN, rats undergoing VA\u2010liposome siHSP47 treatment showed an increment of DNA synthesis of hepatocytes with the concomitant restoration of impaired liver weight and normalization of albumin levels. These results were consistent with the observation that GFP\u00a0+\u00a0EpCAM hepatic progenitor cells transplanted to DMN rat liver, trans\u2010differentiated into GFP\u00a0+\u00a0mature hepatic cells after VA\u2010liposome siHSP47 treatment. Another rodent model also proved regeneration potential of the fibrotic liver in CCl4 administered Sox9CreERT2ROSA26: YFP mice, VA\u2010liposome siHSP47 treatment\u2010induced restoration of liver weight and trans\u2010differentiation of YEP\u00a0+\u00a0Sox9\u00a0+\u00a0cells into YFP\u00a0+\u00a0hepatic cells, although because of relatively mild hepatotoxicity of CCl4, undamaged hepatocytes also proliferated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results demonstrated that regeneration of chronically damaged liver indeed occurs after anti\u2010fibrosis treatment even under continuous exposure to hepatotoxin, which promises a significant benefit of the anti\u2010fibrosis therapy for refractory liver diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15587","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T04:09:57Z","timestamp":1624248597000},"page":"3418-3428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Resolution of fibrosis by siRNA HSP47 in vitamin A\u2010coupled liposomes induces regeneration of chronically injured livers"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6776-4609","authenticated-orcid":false,"given":"Yasushi","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Community Medicine for Gastroenterology and Oncology Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Department of Molecular Target Exploration, School of Medicine Sapporo Medical University  Sapporo Japan"},{"name":"Department of Molecular Therapeutics, Center for Food and Medical Innovation, Institute for the Business\u2010Regional Collaboration Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Molecular Target Exploration, School of Medicine Sapporo Medical University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Molecular Target Exploration, School of Medicine Sapporo Medical University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rai","family":"Shimoyama","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Shonan Kamakura General Hospital  Kamakura 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