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Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of the present study was to test the hypothesis that inhibition of GSK3<jats:italic>\u03b2<\/jats:italic> mediates autophagy to inhibit liver inflammation and protect against ALF. In ALF mice model induced by <jats:sc>d<\/jats:sc>-galactosamine (<jats:sc>d<\/jats:sc>-GalN) and lipopolysaccharide (LPS), autophagy was repressed compared with normal control, and <jats:sc>d<\/jats:sc>-GalN\/LPS can directly induce autophagic flux in the progression of ALF mice. Autophagy activation by rapamycin protected against liver injury and its inhibition by 3-methyladenine (3-MA) or autophagy gene 7 (Atg7) small interfering RNA (siRNA) exacerbated liver injury. The protective effect of GSK3<jats:italic>\u03b2<\/jats:italic> inhibition on ALF mice model depending on the induction of autophagy, because that inhibition of GSK3<jats:italic>\u03b2<\/jats:italic> promoted autophagy <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and inhibition of autophagy reversed liver protection and inflammation of GSK3<jats:italic>\u03b2<\/jats:italic> inhibition. Furthermore, inhibition of GSK3<jats:italic>\u03b2<\/jats:italic> increased the expression of peroxisome proliferator-activated receptor <jats:italic>\u03b1<\/jats:italic> (PPAR<jats:italic>\u03b1<\/jats:italic>), and the downregulated PPAR<jats:italic>\u03b1<\/jats:italic> by siRNA decreased autophagy induced by GSK3<jats:italic>\u03b2<\/jats:italic> inhibition. More importantly, the expressions of autophagy-related gene and PPAR<jats:italic>\u03b1<\/jats:italic> are significantly downregulated and the activity of GSK3<jats:italic>\u03b2<\/jats:italic> is significantly upregulated in liver of ALF patients with hepatitis B virus. Thus, we have demonstrated the new pathological mechanism of ALF that the increased GSK3<jats:italic>\u03b2<\/jats:italic> activity suppresses autophagy to promote the occurrence and development of ALF by inhibiting PPAR<jats:italic>\u03b1<\/jats:italic> pathway.<\/jats:p>","DOI":"10.1038\/cddis.2016.56","type":"journal-article","created":{"date-parts":[[2016,3,24]],"date-time":"2016-03-24T13:55:10Z","timestamp":1458827710000},"page":"e2151-e2151","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Inhibition of glycogen synthase kinase 3\u03b2 promotes autophagy to protect mice from acute liver failure mediated by peroxisome proliferator-activated receptor \u03b1"],"prefix":"10.1038","volume":"7","author":[{"given":"F","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,24]]},"reference":[{"key":"BFcddis201656_CR1","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1053\/jhep.2000.17687","volume":"32","author":"N Rolando","year":"2000","unstructured":"Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R . 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