title: Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge.
abstract: Acute liver injury in the setting of fibrosis is an area of interest in investigations, and remains to be fully elucidated. Previous studies have suggested the beneficial effects of liver fibrosis induced by thioacetamide and partial bile duct ligation against Fas‑mediated acute liver injury. The activation of AKT and extracellular signal-regulated kinase signaling is considered to be crucial in this hepatoprotection. To demonstrate the protection of CCl4‑induced liver fibrosis against lethal challenge, the present study compared the reactivity to lethal doses of D‑galactosamine (D-GalN)/lipopolysaccharide (LPS) between fibrotic mice and control mice groups. The extent of hepatic damage was assessed by survival rate and histopathological analysis. The molecular basis of the fibrosis‑based hepatoprotection was examined, with a particular focus on the translocation and release of high‑mobility group box (HMGB)1 and the inflammatory response triggered by HMGB1. Hepatoprotection induced by fibrosis was demonstrated by improved survival rates (100%, vs. 20%) and improved preservation of liver architecture in fibrotic mice subjected to D‑GalN/LPS, compared with control mice treated in the same way. D‑GalN/LPS evoked the translocation and release of HMGB1, detected by immunohistochemistry, in the control mice, which was significantly inhibited in the fibrotic mice. The gene expression levels of HMGB1‑associated proinflammatory cytokines, including interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α and IL‑12p40, were markedly inhibited in the fibrotic mice when exposed to D‑GalN/LPS. These findings confirmed that CCl4‑based fibrosis induced hepatoprotection, and provided evidence that fibrosis inhibited the translocation and release of HMGB1, and the proinflammatory response triggered by HMGB1. This alleviated liver damage following exposure to D‑GalN/LPS challenge.
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Qingfen
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Kejia
authors.initials: K
authors.lastname: Zu
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Sujun
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Research Department, Beijing Institute of Liver Diseases, Beijing 100069, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Clinical Laboratory Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Lou
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D021381:Protein Transport / Q000187:drug effects
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides