| Author |
Zhang, Xiaohui Bai, Li Chen, Yu Ren, Feng Zu, Kejia Zheng, Sujun Lou, Jinli Duan, Zhongping Li, Junfeng Kong, Ming Liu, Xin Zheng, Qingfen Liu, Shuang |
| Description |
Author Affiliation: Bai L ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Kong M ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Zheng Q ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Zhang X ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Liu X ( Clinical Laboratory Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Zu K ( Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Chen Y ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Zheng S ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Li J ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Ren F ( Research Department, Beijing Institute of Liver Diseases, Beijing 100069, P.R. China.); Lou J ( Clinical Laboratory Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Liu S ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.); Duan Z ( Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China.) |
| 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 Fasmediated 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 CCl4induced liver fibrosis against lethal challenge, the present study compared the reactivity to lethal doses of Dgalactosamine (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 fibrosisbased hepatoprotection was examined, with a particular focus on the translocation and release of highmobility 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 DGalN/LPS, compared with control mice treated in the same way. DGalN/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 HMGB1associated proinflammatory cytokines, including interleukin (IL)1ß, IL6, tumor necrosis factor and IL12p40, were markedly inhibited in the fibrotic mice when exposed to DGalN/LPS. These findings confirmed that CCl4based 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 DGalN/LPS challenge. |
