Research Article Details
| Article ID: | A12150 |
| PMID: | 30581002 |
| Source: | Biochem Biophys Res Commun |
| Title: | Secreted modular calcium-binding protein 2 promotes high fat diet (HFD)-induced hepatic steatosis through enhancing lipid deposition, fibrosis and inflammation via targeting TGF-β1. |
| Abstract: | The molecular mechanism revealing the pathogenesis of non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, remains to be investigated. In the study, we found that secreted modular calcium-binding protein 2 (SMOC2), which belongs to the secreted protein acidic and rich in cysteine (SPARC) family of matricellular proteins, functioned as a positive modulator of NAFLD. SMOC2 expression was markedly up-regulated in human liver samples with NAFLD, and in hepatic tissues of mice fed with HFD. SMOC2 knockout in mice significantly attenuated metabolic disorders, insulin resistance, glucose intolerance and lipid deposition in mice challenged with HFD. Moreover, liver fibrosis induced by HFD was clearly ameliorated by SMOC2 deficiency mainly through inhibiting transforming growth factor (TGF)-β1 expression. Additionally, hepatic inflammatory response triggered by HFD was also improved in SMOC2-knockout mice via inactivating nuclear factor-κB (NF-κB). Mechanically, SMOC2 could interact with TGF-β1, and SMOC2 overexpression markedly increased TGF-β1 in mouse primary hepatocytes, which played an essential role in regulating hepatic steatosis. In conclusion, we provided proof that blocking SMOC2 might be a promising strategy for preventing NAFLD through the interaction with TGF-β1. |
| DOI: | 10.1016/j.bbrc.2018.12.006 |
| 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 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D055 | Calcium | Chemical drug | DB01373 | CAST; COMP; CP; BMP4; MGP | -- | Under clinical trials | Details |