Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2019; 25(24): 3044-3055
Published online Jun 28, 2019. doi: 10.3748/wjg.v25.i24.3044
Effect of NLRC5 on activation and reversion of hepatic stellate cells by regulating the nuclear factor-κB signaling pathway
Yan-Zhen Zhang, Jian-Ning Yao, Lian-Feng Zhang, Chun-Feng Wang, Xue-Xiu Zhang, Bing Gao
Yan-Zhen Zhang, Jian-Ning Yao, Lian-Feng Zhang, Chun-Feng Wang, Xue-Xiu Zhang, Bing Gao, Department of Second Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Zhang YZ, Yao JN, and Zhang LF designed the research; Zhang YZ, Yao JN, and Wang CF performed the research; Zhang LF and Wang CF contributed new reagents and analytic tools; Zhang XX and Gao B analyzed the data; Zhang YZ, Yao JN, Zhang LF, Wang CF, Zhang XX, and Gao B wrote the paper.
Institutional review board statement: The study was approved by the ethics committee of the First Affiliated Hospital of Zhengzhou University.
Institutional animal care and use committee statement: The study was approved by the institutional animal care and use committee of the First Affiliated Hospital of Zhengzhou University.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This is an open-access article that 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/
Corresponding author: Yan-Zhen Zhang, MD, Doctor, Department of Second Gastroenterology, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou 450052, Henan Province, China. zhangyz8848@163.com
Telephone: +86-371-66271117
Received: March 20, 2019
Peer-review started: March 20, 2019
First decision: April 4, 2019
Revised: April 27, 2019
Accepted: June 1, 2019
Article in press: June 1, 2019
Published online: June 28, 2019
Processing time: 101 Days and 5 Hours
ARTICLE HIGHLIGHTS
Research background

Continuous progression of liver fibrosis is the key to the development of chronic liver disease to cirrhosis. The nuclear factor-κB (NF-κB) signaling pathway is closely related to the formation and reversion of hepatic fibrosis. It has been found that NLRC5 is involved in the development of liver fibrosis by regulating the NF-κB signaling pathway and some studies suggest that NLRC5 is a key regulator of liver fibrosis and its reversal, but the role of NLRC5 in liver fibrosis remains unclear.

Research motivation

NLRC5 is highly expressed in immune tissues or organs and involved in the regulation of innate and adaptive immunity by inducing inflammation and cell death. Researches have shown that it may play an important role in the activation and inactivation of hepatocytes, but the research on the mechanism of action fell far behind the immunological study. Our study aimed to investigate the role and mechanism of NLRC5 in liver fibrosis to evaluate its clinical application value.

Research objectives

In this study, we analyzed the expression levels of NLRC5 in liver tissue and LX-2 cells and the activity of NF-κB in hepatic fibrosis after treatment with NLRC5-siRNA. The purpose of this study was to explore the relationship between NLRC5 and the NF-κB signaling pathways during the development and reversal of hepatic fibrosis.

Research methods

Eight-week-old male C57BL/6 mice were randomly divided into groups to establish liver fibrosis and its reversal model. Meanwhile, human hepatic stellate cell (HSC) line LX-2 was cultured in vitro and treated with transforming growth factor-β1 (TGF-β1) and MDI to activate and inactivate the cells. The degree of liver fibrosis and the expression of NLRC5 in mouse tissues and LX-2 cells were detected by qPCR and Western blot. After interfering with NLRC5 by siRNA, the activity of NF-κB in liver fibrosis was detected.

Research results

The expression level of NLRC5 was higher in liver tissue of fibrosis mice and activated HSCs, but decreased in mice with hepatic fibrosis with spontaneous reversion and inactivated HSC cells (P < 0.01). After treatment with NLRC5-siRNA, the activity of the NF-κB signaling pathway was increased in the liver of fibrosis mice and activated HSCs (P < 0.05).

Research conclusions

NLRC5 may play a key role in regulating the progression and reversal of liver fibrosis by negatively regulating the NF-κB signaling pathway, and it is expected to be one of the clinical therapeutic targets.

Research perspectives

NLRC5 plays a physiologically important role in maintaining immune homeostasis, particularly in regulating innate immune responses. Exploring the role and mechanism of NLRC5 and NF-κB in liver fibrosis can provide an important reference for the treatment of liver fibrosis.