Research Article Details
| Article ID: | A18062 |
| PMID: | 27377869 |
| Source: | Clin Exp Immunol |
| Title: | MicroRNA-26a-interleukin (IL)-6-IL-17 axis regulates the development of non-alcoholic fatty liver disease in a murine model. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. MicroRNA 26a (Mir-26a) has been reported to play functions in cellular differentiation, cell growth, cell apoptosis and metastasis. A recent paper indicated that Mir-26a regulated insulin sensitivity and metabolism of glucose and lipids. However, the role of Mir-26a in NAFLD still needs to be investigated further. In our current study, vectors encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered approximately 2 × 107 transforming units of recombinant lentivirus were injected into mice through the tail vein. LV-26a-infected mice were protected from glucose dysmetabolism and showed markedly decreased total liver weight, hepatic triglyceride deposition and serum alanine transaminase (ALT) concentration when compared with LV-Con-treated mice. LV-26a-treated mice also exhibited decreased infiltration of immune cells in the liver - something attributed to reduce infiltration of T cell receptor (TCR)-γδ+ , granulocyte-differentiation antigen-1 (Gr-1)+ cells and CD11b+ cells. Next, we found that Mir-26a inhibited the expression of interleukin (IL)-17 and IL-6 in vivo and in vitro. Furthermore, the decreased expression of IL-17 in the liver tissue induced by Mir-26a was abrogated completely by IL-6 overexpression. The decreased total liver weight, hepatic triglyceride deposition and serum ALT concentration induced by Mir-26a was also abrogated completely by IL-6 over-expression. In conclusion, the Mir-26a-IL-6-IL-17 axis regulates the development of NAFLD in a murine model. |
| DOI: | 10.1111/cei.12838 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| S17 | Genetic therapy | Genetic approaches; genetherapy; Gene therapy | HSD17B13 inhibitor; PNPLA3-rs7 38409 (I148M) variant inhibitor; PNPLA3 expression down-regulator | INI-678; Momelotinib | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |