Liver Fibrosis: Underlying Mechanisms and Innovative Therapeutic Approach. A Review Article

Abstract

Liver fibrosis is considered: “a pathological repairing process in liver injuries leading to extracellular cell matrix (ECM) accumulation evidencing chronic liver diseases”. Chronic viral hepatitis, alcohol consumption, autoimmune diseases as well as non-alcoholic steatohepatitis are from the main causes of liver fibrosis (Lee et al., 2015; Mieli-Vergani et al., 2018). Hepatic stellate cells (HSCs) exist in the sinus space next to the hepatic epithelial cells as well as endothelial cells (Yin et al., 2013). Normally, HSCs are quiescent and mainly participate in fat storage and in the metabolism of vitamin A. HSCs are produced during liver injury and then transformed into myofibroblasts. The activated HSCs resulted in a sequence of events considered as marks fibrosis. The activation of HSCs mostly express alpha smooth muscle actin (α-SMA). Moreover, ECM is synthesized and secreted by HSCs that affects markedly the structure and function of the liver tissue leading to fibrosis (Tsuchida et al., 2017; Han et al., 2020). Hence, activated HSCs are attracting attention as potential targets in liver fibrosis. Many signaling molecules are involved in HSCs activation first and foremost, platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) (Tsuchida et al., 2017; Wang et al., 2020c) as interfering the PDGF or TGF-β signaling pathways is a growing field for liver fibrosis treatment.