Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review).

Galectin-3 is a member of the galectin family, which are ß­galactoside­binding lectins with ≥1 evolutionary conserved carbohydrate­recognition domain. It binds proteins in a carbohydrate­dependent and ­independent manner. Galectin­3 is predominantly located in the cytoplasm; however, it shuttles into the nucleus and is secreted onto the cell surface and into biological fluids including serum and urine. It serves important functions in numerous biological activities including cell growth, apoptosis, pre­mRNA splicing, differentiation, transformation, angiogenesis, inflammation, fibrosis and host defense. Numerous previous studies have indicated that galectin­3 may be used as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease and cancer. With emerging evidence to support the function and application of galectin­3, the current review aims to summarize the latest literature regarding the biomarker characteristics and potential therapeutic application of galectin­3 in associated diseases.

Renal handling of galectin-3 in the general population, chronic heart failure, and hemodialysis.

BACKGROUND: Galectin-3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin-3 levels. We aimed to describe galectin-3 renal handling in HF. METHODS AND RESULTS: In Sprague-Dawley rats, we infused galectin-3 and studied distribution and renal clearance. Furthermore, galectin-3 was measured in urine and plasma of healthy controls, HF patients and hemodialysis patients. To mimic the human situation, we measured galectin-3 before and after the artificial kidney. Infusion in rats resulted in a clear increase in plasma and urine galectin-3. Plasma galectin-3 in HF patients (n=101; mean age 64 years; 93% male) was significantly higher compared to control subjects (n=20; mean age 58 years; 75% male) (16.6 ng/mL versus 9.7 ng/mL, P<0.001), while urinary galectin-3 in HF patients was comparable (28.1 ng/mL versus 35.1 ng/mL, P=0.830). The calculated galectin-3 excretion rate was lower in HF patient (2.3 mL/min [1.5 to 3.4] versus 3.9 mL/min [2.3 to 6.4] in control subjects; P=0.005). This corresponded with a significantly lower fractional excretion of galectin-3 in HF patients (2.4% [1.7 to 3.7] versus 3.0% [1.9 to 5.5]; P=0.018). These differences, however, were no longer significant after correction for age, gender, diabetes, and smoking. HF patients who received diuretics (49%) showed significantly higher aldosterone and galectin-3 levels. Hemodialysis patients (n=105; mean age 63 years; 65% male), without urinary galectin-3 excretion, had strongly increased median plasma galectin-3 levels (70.6 ng/mL). CONCLUSIONS: In this small cross-sectional study, we report that urine levels of galectin-3 are not increased in HF patients, despite substantially increased plasma galectin-3 levels. The impaired renal handling of galectin-3 in patients with HF may explain the described relation between renal function and galectin-3 and may account for the elevated plasma galectin-3 in HF.

Urinary IL-33 and galectin-3 increase in patients with interstitial cystitis/bladder pain syndrome (review).

Interstitial cystitis/bladder pain syndrome (IC/BPS) is an enigmatic chronic disorder characterized by vague bladder pain of variable severity accompanied by urinary symptoms. The pathogenesis and etiology of IC/BPS remain incompletely defined. However, there is an emerging consensus about the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC/BPS. Accumulating evidences have suggested that tissue damage is recognized at the cell level via receptor-mediated detection of intracellular proteins (so-called alarmins) released by the necrotic cells. Among these proteins IL-33, galectin-3 (Gal-3) and advanced glycation end products (AGE), may have an important role because they can be participated as cellular components that stimulate the immune system. We determined IL-33, Gal-3, and AGE in 24-hour urine specimens from patients with IC/BPS and healthy subjects. Study participants included 43 woman with IC/BPS and 29 female volunteers. Urinary IL-33, EGF and Gal-3 levels were measured using an enzyme-linked immunosorbent assay, whereas the content of AGE was quantified by natural AGE-specific fluorescence (Ex. 370 nm, Em. 440 nm). Urinary IL-33, and Gal-3 levels were normalized by urinary creatinine (Cr) levels and compared among subgroups. We have found that the levels of IL-33 and Gal-3 were significantly increased in IC/BPS. The level of the IL-33 in the urine of healthy women was equal to 0.32, while the level of IL-33 in IC/BPS patients increases up to 0.58 (p<0.05). Further, the amounts of urine Gal-3 were also elevated in IC/BPS compared to healthy subjects (0.16 versus 0.07; p>0.01) and AGE-specific fluorescence in urine was increased up to 140% in IC/BPS patients. These data suggest on the participation of IL-33, Gal-3 and AGE in the pathogenesis of IC/BPS.

Galectin-3 in urine of cancer patients: stage and tissue specificity.

PURPOSE: Galectin-3 has been implicated in advanced stage of cancer disease. In the current study we examined the possibility of urinary galectin-3 levels to stage cancer disease and to follow up therapy. EXPERIMENTAL DESIGN: Urine was collected from all types of cancer patients at different stages including patients undergoing radio/chemotherapy. Galectin-3 level was determined by anti-galectin-3 based ELISA and agglutination assays. Immunoblotting and purification on lactosyl affinity column further confirmed the presence of galectin-3. RESULTS: Cancer samples exhibited stage dependent expression of galectin-3 approx. ranging from 1.0 to 3.3, 4.4 to 5.4, 5.4 to 24.7, 13.1 to 31.9, 13.9 to 32.9 ng/mg C (creatinine) for stage I-V, respectively, at P approximately <0.05 level. Galectin-3 levels were decreased by approx. threefolds after 5th day of therapy. CONCLUSIONS: Sample collection being simple and non-invasive, urinary galectin-3 may be used as a potential diagnostic tool for monitoring or follow up of the stage of cancer disease.