Crosstalk network among multiple inflammatory mediators in liver fibrosis

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.

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

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

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

Inflammatory mediator network between cytokines and signaling pathway in liver fibrosis. TGF-β: Transforming growth factor-β; IL: Interleukin.