Elucidating the Role of Galectin-3 in the Recurrence of Primary Sclerosing Cholangitis Post-Liver Transplantation as a Potential Therapeutic Target.

Abstract

Primary sclerosing cholangitis (PSC) occurs in approximately 25% of patients post-liver transplantation (LT) and is associated with significant morbidity and mortality. Hepatic duct cholestasis following recurrent PSC may lead to the development of liver cirrhosis and the need for liver retransplantation. To date, the exact etiology of the recurrence of PSC post-LT remains unknown, and it is not currently possible to predict which patients are at risk for recurrence of PSC. Extracellular Galectin-3 (Gal-3) acts as a damage-associated molecular pattern (DAMP) when released into the extracellular matrix (ECM) by injured liver cells. Gal-3 plays a crucial role in immune responses and inflammation by binding and cross-linking surface proteins of neutrophils and macrophages, facilitating the chemotaxis of immune cells to the site of injury, and activating the macrophage inflammasome complex. In addition, Gal-3, by activation of hepatic satellite cells (HSC) to myofibroblast phenotype, induces profibrotic molecules, such as transforming growth factor beta (TGF-β) and increases the expression of collagens in the ECM, leading to liver fibrogenesis. According to the evidence, targeting Gal-3 may have important therapeutic potential in preventing the progression of recurrence in PSC and cholestatic progression post-LT.