Hepatic inflammatory and fibrotic signaling pathways

Hepatic inflammatory and fibrotic signaling pathways represent a complex network of molecular interactions that drive the progression of chronic liver diseases, such as non-alcoholic steatohepatitis (NASH) and cirrhosis. These pathways involve the activation of hepatic stellate cells (HSCs) into myofibroblasts, a process primarily driven by cytokines such as transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) (Bataller & Brenner, 2005, J. Clin. Invest.). Inflammatory signaling often involves the recruitment of bone marrow-derived macrophages via chemokine receptors like CCR2 and CCR5, as well as the activation of the NF-kappaB and Toll-like receptor 4 (TLR4) pathways (Koyama & Brenner, 2017, J. Clin. Invest.). Therapeutic intervention aims to modulate these pathways through various mechanisms, including the use of farnesoid X receptor (FXR) agonists to regulate bile acid metabolism and inflammation, or apoptosis signal-regulating kinase 1 (ASK1) inhibitors to reduce oxidative stress-induced cell death (Friedman et al., 2018, Nat. Med.). Because this term refers to a collection of integrated pathways rather than a single molecular entity, it is categorized as a biological process group rather than a discrete therapeutic target. Understanding these integrated signals is crucial for developing multi-target or combination therapies for advanced liver fibrosis.

Other names

Liver fibrosis signalingHepatic fibrogenesis pathwaysChronic liver disease inflammatory cascades

Modulation of intracellular and intercellular signaling cascades, such as the TGF-beta, NF-kappaB, and TLR4 pathways, to inhibit the activation of hepatic stellate cells and the recruitment of inflammatory cells.