Published online Jun 28, 2019. doi: 10.3748/wjg.v25.i24.3044
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
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.
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.
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.
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.
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).
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.
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.