{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:43:59Z","timestamp":1790700239009,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:00:00Z","timestamp":1550188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["JP16K19931"],"award-info":[{"award-number":["JP16K19931"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["JP26861078"],"award-info":[{"award-number":["JP26861078"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Rho\u2010kinase (ROCK) inhibitor could ameliorate liver fibrosis by suppressing hepatic stellate cell (HSC) activation. However, because systemic administration of ROCK inhibitor causes serious adverse effects, we developed a drug delivery system selectively delivering ROCK inhibitor to HSCs. Here, we examined whether our developed vitamin A (VA)\u2010coupled liposomal ROCK inhibitor reduced liver fibrosis in rats without causing systemic adverse effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>LX\u20102 HSCs were analyzed for morphological changes and the expression of profibrotic proteins. The inhibitory effects of VA\u2010coupled liposomal ROCK inhibitor on liver fibrosis were confirmed in a rat model of liver fibrosis induced by i.p. injection of carbon tetrachloride. The degree of liver fibrosis, biochemical changes, and survival rates were also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vitamin A\u2010coupled liposomal ROCK inhibitor had an effect at approximately 1\/100 the amount of the free ROCK inhibitor for inhibiting the activation of LX\u20102 cells and caused significant decreases in the expression levels of \u03b1\u2010smooth muscle actin (SMA) and transforming growth factor (TGF)\u2010\u03b21. The degree of liver fibrosis was suppressed by treatment with VA\u2010coupled liposomal ROCK inhibitor, and the expression of \u03b1\u2010SMA and TGF\u2010\u03b21 in liver tissues was also significantly suppressed. In addition, serum levels of alanine aminotransferase and hyaluronic acid were significantly reduced, and there was no decline in kidney function, which has been noted as a systemic adverse effect of ROCK inhibitor. Furthermore, VA\u2010coupled liposomal ROCK inhibitor improved survival rates in rats with liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Vitamin A\u2010coupled liposomal ROCK inhibitor efficiently suppressed liver fibrosis without causing systemic adverse effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13317","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T19:26:19Z","timestamp":1548357979000},"page":"663-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Vitamin A\u2010coupled liposomal Rho\u2010kinase inhibitor ameliorates liver fibrosis without systemic adverse effects"],"prefix":"10.1111","volume":"49","author":[{"given":"Sho","family":"Okimoto","sequence":"first","affiliation":[{"name":"Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences Hiroshima 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