Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Sep 7;25(33):4835-4849.
doi: 10.3748/wjg.v25.i33.4835.

Crosstalk network among multiple inflammatory mediators in liver fibrosis

Han-Jing Zhangdi  1 , Si-Biao Su  1 , Fei Wang  1 , Zi-Yu Liang  1 , Yu-Dong Yan  1 , Shan-Yu Qin  1 , Hai-Xing Jiang  2
Affiliations
Review

Crosstalk network among multiple inflammatory mediators in liver fibrosis

Han-Jing Zhangdi et al. World J Gastroenterol. .

Abstract

Liver fibrosis is the common pathological basis of all chronic liver diseases, and is the necessary stage for the progression of chronic liver disease to cirrhosis. As one of pathogenic factors, inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells, cytokines, and the related signaling pathways. Damaged hepatocytes induce an increase in pro-inflammatory factors, thereby inducing the development of inflammation. In addition, it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis. The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production, which in turn initiate the fibrotic response. Compared with the past, the research on the pathogenesis of liver fibrosis has been greatly developed. However, the liver fibrosis mechanism is complex and many pathways involved need to be further studied. This review mainly focuses on the crosstalk regulatory network among inflammatory cells, cytokines, and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases. Moreover, we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response.

Keywords: Crosstalk network; Cytokine signal pathway; Inflammatory cell; Liver fibrosis.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest.

Figures

Figure 1
Figure 1
Transforming growth factor-β mediated crosstalk network in liver fibrosis. TGF-β is primarily signaled by intracellular Smads. TGF-β: Transforming growth factor-β; HSC: Hepatic stellate cell; NK: Natural killer.
Figure 2
Figure 2
Toll-like receptor mediated crosstalk network in liver fibrosis. Toll-like receptor is a member of DAMPs that recognize pathogen-associated molecules and thereby transmit inflammatory signals that cause inflammatory responses. TLR: Toll-like receptor; MAPK: Mitogen-activated protein kinase; NF-кB: Nuclear factor-кB; HSC: Hepatic stellate cell; DC: Dendritic cells; NK: Natural killer.
Figure 3
Figure 3
STAT3-mediated inflammatory mediator crosstalk network in liver fibrosis. EGFR: Epidermal growth factor receptor; HSC: Hepatic stellate cell; TGF-β: Transforming growth factor-β; MAPK: Mitogen-activated protein kinase; IL: Interleukin.
Figure 4
Figure 4
Inflammatory mediator network between cytokines and signaling pathway in liver fibrosis. TGF-β: Transforming growth factor-β; IL: Interleukin.
See this image and copyright information in PMC

References

    1. Chen L, Brenner DA, Kisseleva T. Combatting Fibrosis: Exosome-Based Therapies in the Regression of Liver Fibrosis. Hepatol Commun. 2018;3:180–192. - PMC - PubMed
    1. Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008;88:125–172. - PMC - PubMed
    1. Li T, Shi Z, Rockey DC. Preproendothelin-1 expression is negatively regulated by IFNγ during hepatic stellate cell activation. Am J Physiol Gastrointest Liver Physiol. 2012;302:G948–G957. - PMC - PubMed
    1. Chen L, Ji Z, Duan L, Zhu D, Chen J, Sun X, Yu Y, Duan Y. rSJYB1 inhibits collagen type I protein expression in hepatic stellate cells via down-regulating activity of collagen α1 (I) promoter. J Cell Mol Med. 2019;23:3676–3682. - PMC - PubMed
    1. Miao CG, Yang YY, He X, Huang C, Huang Y, Zhang L, Lv XW, Jin Y, Li J. Wnt signaling in liver fibrosis: progress, challenges and potential directions. Biochimie. 2013;95:2326–2335. - PubMed

MeSH terms