Figure 1.

Cascade of fibrotic process activation in liver diseases. Physiologically, there are four distinct phases, injury, hemostasis, inflammatory phase, and maturation phase, which lead to the regeneration of damaged tissues following an injury. In the liver, when the wound response becomes pathogenic, the generation of fibrotic tissue replaces liver tissue and impairs organ function. The onset of fibrosis occurs with the activation of quiescent HSCs, i.e., resident mesenchymal cells. These cells differentiate into myofibroblasts and begin to secrete ECM constituents, particularly increasing the expression of fibrotic collagens (i.e., types III, IV, and V), fibronectins, and hyaluronic acid. Other pro-fibrotic components have also been implicated as endogenous DAMPs recognized by PRRs (pattern recognition receptors). MMPs, expressed by a variety of immune and non-immune cells, degrade ECM components, including collagen and fibronectin, making them essential for tissue remodeling. The balance between MMPs and TIMPs in the liver plays a vital role in the induction of liver fibrosis.