Unravelling TGF-β Signaling and Integrin-Mediated Mechanotransduction: Key Drivers of Liver Fibrosis

Mechanotransduction pertains to the cellular process of transforming mechanical cues into biochemical retort, which is crucial in liver biology and influences the development of liver diseases, including fibrosis and cancer. The activation of integrin-mediated signaling pathways is a chief mechanism in liver fibrosis, mounting the extracellular matrix (ECM) to the cytoskeleton and ensuing in alterations in cell functioning and phenotype. Hepatic stellate cells (HSCs), portal fibroblasts, and liver sinusoidal endothelial cells are prime targets of mechanical forces within the liver, demonstrating phenotypic changes in response to alterations in extracellular matrix (ECM) stiffness. The transforming growth factor-beta (TGF-β) signaling pathway is center to this process, arbitrating fibrosis via both canonical and non-canonical SMAD-dependent and independent mechanisms. TGF-β signaling urges collagen deposition and HSC triggering, two momentous aspects of liver fibrosis. The complex interplay among cytoskeletal remodeling, TGF-β signaling, and Mechanotransduction in liver fibrosis is the central theme of this review. We also addressed potential therapeutic targets that are currently being studied in clinical settings and recognized as possible therapeutic targets, particularly those in the TGF-β signaling pathway. Procuring insights into these molecular processes can help develop innovative treatment approaches that target liver fibrosis and other chronic liver illnesses.