Galectin-3 is a protein found throughout the human body, belonging to the galectin family. These proteins bind to specific sugar molecules, allowing galectin-3 to act as a molecular messenger that influences how cells interact and behave. Its presence in numerous tissues and organs underscores its broad involvement in biological processes.
The Basic Nature of Galectin 3
Galectin-3 is a lectin that interacts with beta-galactoside sugars found on other proteins or cell surfaces. This protein is approximately 30 kDa in size and possesses a carbohydrate-recognition-binding domain (CRD) of about 130 amino acids. Galectin-3 is encoded by the LGALS3 gene on chromosome 14 and can be found in various cellular locations, including the nucleus, cytoplasm, mitochondria, cell surface, and extracellular space.
Under normal conditions, galectin-3 regulates many physiological processes. It mediates cell-to-cell communication and cell-matrix interactions, which are fundamental for tissue organization and function. The protein is involved in regulating cell growth, differentiation, and programmed cell death (apoptosis), sometimes inhibiting it to promote cell survival. Galectin-3 also contributes to balanced immune responses and tissue repair.
When Galectin 3 Becomes Problematic
Galectin-3’s overexpression or dysregulation can contribute to various disease processes. This shift is observed in chronic inflammation, fibrosis, and abnormal cell growth.
In chronic inflammation, galectin-3 can perpetuate the inflammatory response by recruiting immune cells, such as macrophages, to injury sites and activating pro-inflammatory pathways. This sustained inflammation can lead to tissue damage and dysfunction. For example, in non-alcoholic fatty liver disease (NAFLD), galectin-3 is involved in the inflammatory response that can lead to liver scarring.
Galectin-3 also plays a significant role in fibrosis, which is the excessive scarring of tissues. It promotes the proliferation of fibroblasts and the deposition of collagen, leading to stiffening and impaired function of organs like the heart, kidneys, liver, and lungs. In heart failure, increased galectin-3 expression is linked to heightened fibrosis and inflammation, contributing to adverse ventricular remodeling. Genetic studies in mice have shown that the absence of galectin-3 can prevent or reduce fibrosis development in organs like the liver.
Dysregulated galectin-3 contributes to abnormal cell proliferation, survival, and migration, particularly in cancer. It can promote tumor growth by reducing cell death and encouraging the formation of new blood vessels that supply the tumor. Galectin-3 also enhances the ability of cancer cells to invade surrounding tissues and metastasize to distant sites. It can even help tumor cells evade the immune system, protecting them from immune cell attack.
Galectin 3 as a Marker and Target
The presence of galectin-3 in various bodily fluids, such as blood, makes it a valuable biomarker for certain health conditions. Elevated levels of galectin-3 in the blood can indicate that the body is working harder to address issues like infection, injury, or long-term health problems. Specifically, galectin-3 is recognized as a prognostic marker for heart failure, with higher concentrations linked to increased risks of mortality and re-hospitalization.
Measuring galectin-3 levels can provide insights into the progression of cardiac fibrosis and inflammation, hallmarks of heart remodeling in heart failure. Galectin-3 offers the advantage of being more stable and less affected by hemodynamic changes compared to some other biomarkers. The US Food and Drug Administration has approved galectin-3 as a soluble biomarker for cardiac fibrosis to detect cardiac tissue remodeling.
Beyond its diagnostic and prognostic utility, galectin-3 is also being explored as a potential therapeutic target. Scientists are developing compounds, such as carbohydrate-based drugs, that inhibit galectin-3’s binding activity to counteract its detrimental roles in disease. This approach aims to reduce inflammation, prevent excessive scarring, and potentially enhance the body’s immune response against cancer cells. Clinical trials are investigating galectin-3 inhibitors for conditions like non-alcoholic steatohepatitis (MASH) cirrhosis and various cancers, aiming to modulate its activity for therapeutic benefit.