Hepatic inflammation and fibrosis: Functional links and key pathways

Abstract

Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty and autoimmune origin. Inflammation is typically present in all disease stages, and associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. In the past decade, numerous studies have contributed to improved understanding of the links between hepatic inflammation and fibrosis. Here, we review mechanisms that link inflammation with the development of liver fibrosis, focusing on the role of inflammatory mediators in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis and fibrosis regression. We will summarize the contributions of different inflammatory cells, including hepatic macrophages, T- and B-lymphocytes, NK cells and platelets, as well as key effectors such as cytokines, chemokines, and damage-associated molecular patterns. Furthermore, we will discuss the relevance of inflammatory signaling pathways for clinical liver disease and for the development of anti-fibrogenic strategies.

Interspecies NASH disease activity whole-genome profiling identifies a fibrogenic role of PPARα-regulated dermatopontin

“…This conclusion was supported by filtering this list of 34 upregulated genes against ChIP-X databases, showing that their upstream regulatory regions contain bona fide binding sites for PPARs and/or RunX2 and/or Smad transcription factors ( Figure 2C), all involved in HSC responses to liver injury (41). Of note, 20 of the 34 upregulated genes display cell-specific expression in normal mouse liver, 8 of them being strongly expressed in HSCs (Figure 2A; refs.…”

Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients

“…42,43 Several studies stated the important role of TLR-3 in the pathophysiology of a variety of liver diseases [44][45][46] ; TLR-3 is widely expressed on all types of liver cells, including hepatocytes, 47 stellate cells, 48 sinusoidal endothelial cells, 49 Kupffer cells, biliary epithelial cells, 50 and immune cells as natural killer cells, natural killer T-cells, 51 and liver lymphocytes. 49 Animal studies reported that TLR-3 plays a dual role of having a negative or positive effect in liver injury and fibrosis.…”

Long Non-coding RNA Growth Arrest-specific Transcript 5 (GAS5) Inhibits Liver Fibrogenesis through a Mechanism of Competing Endogenous RNA

“…The activation of hepatic stellate cells (HSCs) 3 is generally considered to be a pivotal step in the initiation, as well as the progression, of liver fibrosis (1). Therefore, the inhibition of HSC activation is regarded as a potential therapeutic target for liver fibrosis.…”