From the Guidelines
Galectin-3 plays a crucial role in sepsis and other ailments, serving as a biomarker and mediator in various pathological processes, including inflammation, fibrosis, and immune suppression. The protein's involvement in sepsis is complex, with a dual role in promoting inflammatory responses during early sepsis and contributing to immune suppression in late-stage sepsis 1. In other diseases, such as cardiovascular diseases, galectin-3 drives cardiac fibrosis and remodeling, making it a valuable prognostic marker for heart failure 1. It also promotes fibrosis in kidney disease, liver cirrhosis, and pulmonary fibrosis by activating fibroblasts and increasing collagen production 1. In cancer, galectin-3 facilitates tumor growth, metastasis, and immune evasion 1. Clinically, elevated galectin-3 levels correlate with sepsis severity and mortality risk, with normal levels typically below 17.8 ng/mL 1. Some key points to consider include:
- Galectin-3's role in sepsis and other diseases makes it a promising therapeutic target, with galectin-3 inhibitors currently under investigation for treating conditions characterized by inflammation and fibrosis.
- Understanding galectin-3's mechanisms helps explain disease progression and offers potential for developing targeted treatments for sepsis and other inflammatory conditions.
- The protein's involvement in various pathological processes highlights the importance of early recognition and treatment of sepsis, as well as the need for adjunctive therapies to modulate the immune response and prevent organ failure.
- Further research is needed to fully understand the role of galectin-3 in sepsis and other diseases, and to develop effective therapeutic strategies for targeting this protein.
From the Research
Role of Galectin-3 in Sepsis
- Galectin-3 plays a critical role in sepsis outcome, with serum Galectin-3 concentration increasing in patients with septic shock and mice undergoing sepsis induced by cecal ligation and puncture (CLP) 2.
- Mice deficient in Galectin-3 (Gal-3 KO) are more resistant to sepsis induced by CLP, showing lower levels of biochemical markers and neutrophil infiltration for organ injury/dysfunction than those observed in wild-type mice (WT) 2.
- Galectin-3 inhibits neutrophil migration into the infectious focus, which promotes the bacterial spread and worsens the outcome of sepsis 2, 3.
Role of Galectin-3 in Other Ailments
- Galectin-3 functions as an alarmin, playing a pathogenic role in sepsis development in murine respiratory tularemia 3.
- Galectin-3 is associated with several diseases, including fibrosis, heart failure, atherosclerosis, and diabetes mellitus, with its expression induced under conditions of tissue injury or stress 4.
- Galectin-3 is a useful biomarker in prognosis and risk stratification of heart failure, especially in HF with preserved ejection fraction, and is considered a culprit protein in the development of cardiac fibrosis in HF 5, 6.
Mechanisms of Galectin-3 Activation and Inhibition
- Galectin-3 undergoes "activation" which significantly broadens the spectrum of biological activity mainly by modifying its carbohydrate-binding properties 4.
- Self-interactions of Galectin-3 appear to play a crucial role in regulating the extracellular activities of this protein, however there is limited and controversial data on the mechanisms involved 4.