{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:31:45Z","timestamp":1790659905580,"version":"4.1.0"},"reference-count":0,"publisher":"American Scientific Publishers","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["j biomed nanotechnol"],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:p>Titanium dioxide (TiO<jats:sub>2<\/jats:sub>) and nano-sized titanium dioxide (nano-TiO<jats:sub>2<\/jats:sub>), which are used in food production, may be harmful to the body. Long-term exposure to nano-TiO<jats:sub>2<\/jats:sub> can lead to hepatic injury; however, the effect of nano-TiO<jats:sub>2<\/jats:sub> on liver fibrosis\n and the underlying mechanism remain unclear. The TGF-<jats:italic>\u03b2<\/jats:italic>\/Smad\/MAPK\/Wnt signaling pathway is important for tissue fibrosis. In this study, mice were fed nano-TiO<jats:sub>2<\/jats:sub> (2.5, 5, and 10 mg\/kg body weight) for nine consecutive months to investigate its effect on liver fibrosis.\n Nano-TiO<jats:sub>2<\/jats:sub> induced hepatic inflammatory cell infiltration and hepatic fibrosis and upregulated the expression of HIF-1<jats:italic>\u03b1<\/jats:italic> (+75-fold to +2.38-fold), Wnt3 (+12% to +135%), Wnt4 (1.33-fold to 6-fold), NF-<jats:italic>\u03ba<\/jats:italic>B (+3.13% to +34.38%), TGF-<jats:italic>\u03b2<\/jats:italic>1 (+1307-fold\n to +1.85-fold), TGF-<jats:italic>\u03b2<\/jats:italic>1R (+0.8-fold to 1.33-fold), Smad-2 (+0.58-fold to +1.58-fold), ILK (+0.43-fold to +1.19-fold), ECM (+1.82-fold to 2.36-fold), calpain 2 (+0.11-fold to +0.78-fold), <jats:italic>\u03b1<\/jats:italic>-SMA (+0.63-fold to +1.56-fold), c-Myc (+0.27-fold to +0.46-fold), and collagen\n I (+8% to +36%), and increased the phosphorylation level of p38MAPK (+66.67% to +153.33%) in inflammatory and fibrotic liver tissues, whereas it downregulated cyclin D (\u20136.25% to \u201343.75%) and decreased the phosphorylation levels of GSK-3<jats:italic>\u03b2<\/jats:italic> (\u20133.12% to \u201346.88%)\n and <jats:italic>\u03b2<\/jats:italic>-catenin (\u201319.57% to \u201345.65%). These results indicate that hepatic fibrosis induced by nano-TiO<jats:sub>2<\/jats:sub> is mediated by the TGF-<jats:italic>\u03b2<\/jats:italic>\/Smads\/MAPK\/Wnt signaling pathway. This study provides insight into the mechanism underlying hepatic toxicity induced\n by nano-TiO<jats:sub>2<\/jats:sub> .<\/jats:p>","DOI":"10.1166\/jbn.2020.2921","type":"journal-article","created":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T04:30:45Z","timestamp":1599971445000},"page":"616-625","source":"Crossref","is-referenced-by-count":36,"title":["Liver Inflammation and Fibrosis Induced by Long-Term Exposure to Nano Titanium Dioxide (TiO<sub>2<\/sub>) Nanoparticles in Mice and Its Molecular Mechanism"],"prefix":"10.1166","volume":"16","author":[{"given":"Fashui","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguan","family":"Ze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"17","container-title":["Journal of Biomedical Nanotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ingentaconnect.com\/content\/asp\/jbn\/2020\/00000016\/00000005\/art00005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T04:30:52Z","timestamp":1599971452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ingentaconnect.com\/content\/10.1166\/jbn.2020.2921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5,1]]}},"alternative-id":["1550-7033(20200501)16:5L.616;1-"],"URL":"https:\/\/doi.org\/10.1166\/jbn.2020.2921","relation":{},"ISSN":["1550-7033"],"issn-type":[{"value":"1550-7033","type":"print"}],"subject":[],"published":{"date-parts":[[2020,5,1]]}}}