Table 1.
Conditions and diseases, listed in alphabetical order, in which a possible role of Gal-3 was postulated in pathogenesis, diagnosis, prognosis, stratification for therapy and in therapy.
| Letter Names | Disease/Condition | Possible Role in Pathogenesis | Possible Role in Diagnosis/Prognosis | Possible Role in Patients Stratification for Therapy | Possible Role in Therapy |
|---|---|---|---|---|---|
| A | Asthma | Gal-3 positive patients are more responsive to omalizumab | |||
| Atherosclerosis | Gal-3 is expressed in advanced atherosclerotic lesions | ||||
| Atopic Dermatitis | Gal-3 released by PMNs amplifies IgE production | Gal-3 inhibitors used in a phase 2 controlled trial for treatment of severe atopic dermatitis | |||
| B | Blood test | Blood assays (ELISA) to predict outcome of acute and chronic heart failure | |||
| C | Cancer | Gal-3 controls oncogenesis, cancer progression and metastasis | Diagnostic role in thyroid, prostate, and ovarian cancers | Clinical trials using Gal-3 inhibitors for melanoma and large B-cell lymphoma | |
| Cerebral infarction | Serum levels of Gal-3 are increased in ischemic brain damage | Measurement of serum Gal-3 levels may help in diagnosis of cerebral infarction | |||
| COPD | Gal-3 levels measured in BAL are reduced in healthy smokers | In patients with COPD serum Gal-3 levels may predict right ventricular dysfunction and acute exacerbation of COPD | |||
| D | Degenerative Aortic Stenosis |
Serum Gal-3 levels may be useful in stratification for therapy in elderly patients affected by degenerative aortic stenosis | |||
| Diabetes Mellitus | Conflicting results: Gal-3 plays a rotective role; Gal-3 is a risk factor for vascular/renal/cardiac complications |
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| E | Endometriosis | Gal-3 is overexpressed in endometriotic tissue | |||
| Enteric nervous system | Gal-3 is crucial mediator of the GI damage observed after brain injuries, at the level of enteric neuronal cells | ||||
| Encephalitis | Gal-3 is involved in various types of CNS inflammation and in particular in viral encephalitis | ||||
| F | Fibrosis | Gal-3 is key regulator of chronic inflammation and tissue fibrogenesis | Serum Gal-3 levels are increased in fibrosis affecting the liver, the kidney, the lung, the heart, the nervous system and in the systemic sclerosis. In such conditions Gal-3 has been proposed as a new prognostic factor | ||
| G | Gastritis | Gal-3 is upregulated in gastric epithelial cells following adhesion of Helicobacter pylori | Experimental evidence indicates that administration of extracellular recombinant Gal-3 (rGal-3) is able to inhibit the adhesion of Helicobacter pylori to the gastric epithelial cells | ||
| H | Heart | Serum Gal-3 levels are associated with mortality in patients with chronic heart failure | Gal-3 is useful as a marker for stratification for therapy (rosuvastatin and cardiac resynchronization) in patient with heart failure | ||
| HIV infection | Gal-3 is associated with early stages of HIV infection and is involved in the host response to HIV infection. | ||||
| I | Inflammation | Gal-3 is involved in many processes during both acute and chronic inflammatory response | |||
| Interstitial lung disease | Gal-3 is increased in the serum of patients affected by IPF, and is associated with decreased lung volumes and altered gas exchange | A novel target therapy for IPF was proposed using a Gal-3 inhibitor (TD139) formulated for inhalation and a clinical trial process was started | |||
| J | Juvenile Idiopathic Arthritis | Gal-3 serum levels are increased in children affected by JIA and correlate with disease activity | |||
| K | Kidney | Gal-3 serum levels are upregulated in diabetic nephropathy and acute renal failure | Experimental evidence indicates that pharmacologic inhibition of Gal-3 with MCP is protective toward nephropathy. Another Gal-3 inhibitor, the GCS-100, significantly improved the eGFR in patients with CKD stage 3b. | ||
| L | Liver fibrosis | Gal-3 plays a critical role in hepatic stellate cells activation to a myofibroblast phenotype, a critical event in extracellular matrix deposition and in the development of cirrhosis | A Gal-3 antagonist, named GR-MD-02, is current on a phase 2 Clinical Trial to prevent progression toward cirrhosis in patients with NASH | ||
| M | Mortality | Gal-3 is associated with risk of coronary heart disease, CVD mortality, and all-cause mortality | |||
| N | Non-alcoholic steatohepatitis (NASH) | Experimental evidence indicates that mice lacking the Gal-3 gene are resistant to liver fibrosis | The specific Gal-3 inhibitor, named GR-MB-02, is on Phase 2 Clinical Trial for the treatment of advanced fibrosis due to NASH | ||
| O | Obesity | Gal-3 is expressed in all types of macrophages that permeate white adipose tissue and it is an important regulator of their polarization and activity. Gal3 can bind directly to the insulin receptor (IR) and inhibit downstream IR signaling. | Experimental evidence in mice indicates that inhibition of Gal-3 improves insulin sensitivity | ||
| P | Pneumonia | Gal-3 is involved in the recruitment of neutrophils during lung infections with Streptococcus pneumoniae | Experimental evidence indicates that exogenous administration of Gal-3 to mice has a direct antimicrobial, bacteriostatic effect on Streptococcus pneumonia | ||
| Pulmonary hypertension | Conflicting results:Gal-3 plasma levels are decreased in patients with PAH;Gal-3 plasma levels are increased in PAH independently to etiology and are are associated with severity of PAH | ||||
| Plaque Psoriasis | Gal-3 is expressed in a high proportion of Langerhans cells from skin punch biopsies, obtained from lesional plaque-type psoriatic skin | An open-label phase 2a clinical trial is ongoing using the Gal-3 antagonist GR-MD-02 for the treatment of psoriasis | |||
| Q | Q Fever | Glactin-3 is a sensor of damage caused by the Coxiella burnetii | |||
| R | Rheumatoid Arthritis | Gal-3 plays a key role as pro-inflammatory mediator in RA | Gal-3 serum level has been proposed as a predictive marker of future RA | Experimental evidence indicates that therapeutic intra-articularly administration of lentiviral vectors encoding Gal-3 small hairpin RNA (shRNA), in rats with collagen-induced arthritis, significantly ameliorates disease activity | |
| S | Sepsis | Serum Gal-3 levels may represent a useful marker to predict mortality in patients affected by sepsis | Experimental evidence indicates that Gal-3 may represent a potential target for treatment of sepsis, at least for that induced by Francisella novicida | ||
| Systemic Sclerosis | Serum Gal-3 levels correlate with the developmental process of skin sclerosis and of digital ulcers in diffuse cutaneous SSc | Gal-3 appears to be a reliable biomarker to predict all-cause mortality in patients affected by SSc | |||
| T | Target therapy | Gal-3 is involved in numerous degenerative processes within the body, including cancer proliferation/metastasis, heart failure, atherosclerosis, diabetes, chronic inflammation, fibrosis and related organ failure. | Numerous compounds that are able to inhibit Gal-3 function have been proposed and are currently in Clinical Trials for many different diseases/conditions | ||
| U | Urinary tract infections | Gal-3 plays a role in urinary tract viral and bacterial infections in humans | |||
| V | Venous Thrombosis | Serum levels of Gal-3 and of Gal-3 binding protein are elevated in the course of venous thrombosis | |||
| W | Wound Healing | Gal-3 plays a key player in the re-epithelialization of wounds in many different tissues, including the cornea, the skin and the GI tract | |||
| X | X syndrome of the heart | Serum Gal-3 levels are significantly higher in the CSX patients in comparison with the healthy controls | |||
| Y | Yeast infection-Candidiasis | Gal-3 is present in the fungal granulomata, it binds to Candida albicans in a carbohydrate-specific manner and it displays a direct fungicidal activity | Experimental evidence indicates that the inhibition of Gal-3, obtained by knocking down the gene, by silencing its expression or by administration of the specific inhibitor TD139 is able to inhibit neutrophil reactive oxygen species (ROS) production and enhance the ability of neutrophils to kill Candida albicans | ||
| Z | Zoster-related pain (allodynia) | Gal-3 is involved in the process of Wallerian degeneration distal to the injury and subsequent axonal regrowth and functional re-innervation | Experimental evidence indicates that in mice the intrathecal administration of the Gal-3 inhibitor modified citrus pectin (MCP) is able to significantly attenuate neurophathic pain |