Unraveling the pathophysiologic role of galectin‐3 in chronically injured liver

Abstract Galectin‐3 (Gal‐3) previously referred to as S‐type lectins, is a soluble protein that specifically binds to β‐galactoside carbohydrates with high specificity. Gal‐3 plays a pivotal role in a variety of pathophysiological processes such as cell proliferation, inflammation, differentiation, angiogenesis, transformation and apoptosis, pre‐mRNA splicing, metabolic syndromes, fibrosis, and host defense. The role of Gal‐3 has also been implicated in liver diseases. Gal‐3 is activated upon a hepatotoxic insult to the liver and its level has been shown to be upregulated in fatty liver diseases, inflammation, nonalcoholic steatohepatitis, fibrosis, cholangitis, cirrhosis, and hepatocellular carcinoma (HCC). Gal‐3 directly interacts with the NOD‐like receptor family, pyrin domain containing 3, and activates the inflammasome in macrophages of the liver. In the chronically injured liver, Gal‐3 secreted by injured hepatocytes and immune cells, activates hepatic stellate cells (HSCs) in a paracrine fashion to acquire a myofibroblast like collagen‐producing phenotype. Activated HSCs in the fibrotic liver secrete Gal‐3 which acts via autocrine signaling to exacerbate extracellular matrix synthesis and fibrogenesis. In the stromal microenvironment, Gal‐3 activates cancer cell proliferation, migration, invasiveness, and metastasis. Clinically, increased serum levels and Gal‐3 expression were observed in the liver tissue of nonalcoholic steatohepatitis, fibrotic/cirrhotic, and HCC patients. The pathological role of Gal‐3 has been experimentally and clinically reported in the progression of chronic liver disease. Therefore, this review discusses the pathological role of Gal‐3 in the progression of chronic liver diseases.