Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2015; 21(46): 13055-13063
Published online Dec 14, 2015. doi: 10.3748/wjg.v21.i46.13055
Inhibition of sphingosine kinase 1 ameliorates acute liver failure by reducing high-mobility group box 1 cytoplasmic translocation in liver cells
Yan-Chang Lei, Ling-Ling Yang, Wen Li, Pan Luo, Pei-Fen Zheng
Yan-Chang Lei, Department of Infectious Diseases, Zhejiang Hospital, Hangzhou 310013, Zhejiang Province, China
Yan-Chang Lei, Ling-Ling Yang, Wen Li, Pan Luo, Infectious Disease Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Pei-Fen Zheng, Department of Gastroenterology, Zhejiang Hospital, Hangzhou 310013, Zhejiang Province, China
Author contributions: Lei YC designed the research; Lei YC, Yang LL, Li W, Luo P, and Zheng PF performed the research and analyzed the data; Lei YC and Zheng PF wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81160065.
Institutional review board statement: The study was reviewed and approved by Zhejiang hospital Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Zhejiang Hospital (IACUC protocol number: 126).
Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pei-Fen Zheng, Chief Physician, Department of Gastroenterology, Zhejiang Hospital, 12 Lingyin Road, Hangzhou 310013, Zhejiang Province, China. ycleihust@sina.com
Telephone: +86-571-81595081 Fax: +86-571-87980175
Received: May 24, 2015
Peer-review started: May 29, 2015
First decision: June 25, 2015
Revised: August 9, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: December 14, 2015
Core Tip

Core tip: Recent studies demonstrated that sphingosine kinase 1 (Sphk1) plays a critical role in sepsis-induced inflammatory responses and high-mobility group box 1 (HMGB1) cytoplasmic translocation has an important role in acute liver failure (ALF). The finding that SphK1 is able to mediate the secretion of proinflammatory mediators prompted us to investigate its role in systemic inflammatory response caused by ALF. In the present study, we demonstrated that SphK1 was critical in D-galactosamine/lipopolysaccharide-induced ALF in mice and that inhibition of SphK1 ameliorated ALF by reducing HMGB1 cytoplasmic translocation in liver cells in this animal model. Our findings suggest that inhibition of SphK1 might be a potential therapeutic strategy for ALF.