Research Article Details
| Article ID: | A44444 |
| PMID: | 28618839 |
| Source: | Crit Rev Biochem Mol Biol |
| Title: | Sphingosine kinase and sphingosine-1-phosphate in liver pathobiology. |
| Abstract: | Over 20 years ago, sphingosine-1-phosphate (S1P) was discovered to be a bioactive signaling molecule. Subsequent studies later identified two related kinases, sphingosine kinase 1 and 2, which are responsible for the phosphorylation of sphingosine to S1P. Many stimuli increase sphingosine kinase activity and S1P production and secretion. Outside the cell, S1P can bind to and activate five S1P-specific G protein-coupled receptors (S1PR1-5) to regulate many important cellular and physiological processes in an autocrine or paracrine manner. S1P is found in high concentrations in the blood where it functions to control vascular integrity and trafficking of lymphocytes. Obesity increases blood S1P levels in humans and mice. With the world wide increase in obesity linked to consumption of high-fat, high-sugar diets, S1P is emerging as an accomplice in liver pathobiology, including acute liver failure, metabolic syndrome, control of blood lipid and glucose homeostasis, nonalcoholic fatty liver disease, and liver fibrosis. Here, we review recent research on the importance of sphingosine kinases, S1P, and S1PRs in liver pathobiology, with a focus on exciting insights for new therapeutic modalities that target S1P signaling axes for a variety of liver diseases. |
| DOI: | 10.1080/10409238.2017.1337706 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |