{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:47:16Z","timestamp":1790282836849,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T00:00:00Z","timestamp":1495152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>Activation of hepatic stellate cells (HSCs) is the effector factor of hepatic fibrosis and hepatocellular carcinoma (HCC) development. Accumulating evidence suggests that retinoic acids (RAs), derivatives of vitamin A, contribute to prevention of liver fibrosis and carcinogenesis, however, regulatory mechanisms of RAs still remain exclusive. To elucidate RA signaling pathway, we previously performed a genome\u2010wide screening of RA\u2010responsive genes by in silico analysis of RA\u2010response elements, and identified 26 RA\u2010responsive genes. We found that thioredoxin interacting protein (TXNIP), which inhibits antioxidant activity of thioredoxin (TRX), was downregulated by <jats:italic>all\u2010trans<\/jats:italic> retinoic acid (ATRA). In the present study, we demonstrate that ATRA ameliorates activation of HSCs through TXNIP suppression. HSC activation was attenuated by TXNIP downregulation, whereas potentiated by TXNIP upregulation, indicating that TXNIP plays a crucial role in activation of HSCs. Notably, we showed that TXNIP\u2010mediated HSC activation was suppressed by antioxidant N\u2010acetylcysteine. In addition, ATRA treatment or downregulation of TXNIP clearly declined oxidative stress levels in activated HSCs. These data suggest that ATRA plays a key role in inhibition of HSC activation via suppressing TXNIP expression, which reduces oxidative stress levels.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25921","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T05:57:19Z","timestamp":1490162239000},"page":"607-616","source":"Crossref","is-referenced-by-count":41,"title":["<i>All\u2010trans<\/i> retinoic acid ameliorates hepatic stellate cell activation via suppression of thioredoxin interacting protein expression"],"prefix":"10.1002","volume":"233","author":[{"given":"Hiroki","family":"Shimizu","sequence":"first","affiliation":[{"name":"Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine Tottori University Yonago 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