Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2016; 22(38): 8519-8527
Published online Oct 14, 2016. doi: 10.3748/wjg.v22.i38.8519
Embryonic liver fordin is involved in glucose glycolysis of hepatic stellate cell by regulating PI3K/Akt signaling
Wei Tu, Jin Ye, Zhi-Jun Wang
Wei Tu, Department of Gastroenterology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Wei Tu, Institute of Liver Diseases, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Jin Ye, Zhi-Jun Wang, Department of Gastroenterology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Jin Ye, Zhi-Jun Wang, Institute of Liver Diseases, Union Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Tu W performed the majority of experiments and analyzed the data; Wang ZJ participated equally in treatment of animals; Ye J designed and coordinated the research; Wang ZJ wrote the paper.
Supported by National Natural Science Foundation of China, No. 81300329 and No. 81401992.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Institute of Laboratory Animal Sciences, Huazhong University of Science and Technology, Wuhan, China
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional unpublished data are available.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: Zhi-Jun Wang, MD, PhD, Department of Gastroenterology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology, 1277 Jiefang Road, Jianghan District, Wuhan 430022, Hubei Province, China. xhwzj@aliyun.com
Telephone: +86-27-85726818 Fax: +86-27-85726818
Received: June 4, 2016
Peer-review started: June 4, 2016
First decision: July 12, 2016
Revised: July 27, 2016
Accepted: August 19, 2016
Article in press: August 19, 2016
Published online: October 14, 2016
Processing time: 130 Days and 1.6 Hours
Abstract
AIM

To investigate the role of embryonic liver fordin (ELF) in liver fibrosis by regulating hepatic stellate cells (HSCs) glucose glycolysis.

METHODS

The expression of ELF and the glucose glycolysis-related proteins were evaluated in activated HSCs. siRNA was used to silence ELF expression in activated HSCs in vitro and the subsequent changes in PI3K/Akt signaling and glucose glycolysis-related proteins were observed.

RESULTS

The expression of ELF increased remarkably in HSCs of the fibrosis mouse model and HSCs that were cultured for 3 wk in vitro. Glucose glycolysis-related proteins showed an obvious increase in the activated HSCs, such as phosphofructokinase, platelet and glucose transporter 1. ELF-siRNA, which perfectly silenced the expression of ELF in activated HSCs, led to the induction of glucose glycolysis-related proteins and extracellular matrix (ECM) components. Moreover, pAkt, which is an important downstream factor in PI3K/Akt signaling, showed a significant change in response to the ELF silencing. The expression of glucose glycolysis-related proteins and ECM components decreased remarkably when the PI3K/Akt signaling was blocked by Ly294002 in the activated HSCs.

CONCLUSION

ELF is involved in HSC glucose glycolysis by regulating PI3K/Akt signaling.

Keywords: Liver fibrosis; Embryonic liver fordin; PI3K/Akt signaling; Hepatic stellate cells; Glucose glycolysis

Core tip: The metabolism of activated hepatic stellate cells (HSCs) was reprogrammed. Silence of embryonic liver fordin (ELF) led to the inhibition of PI3K/Akt signaling and decrease of glycolysis in activated HSCs. Glucose glycolysis of activated HSCs was regulated by ELF through PI3K/Akt signaling The present study indicated that metabolism of HSCs may be a novel target for the diagnosis and treatment of liver cirrhosis in clinical practice.