Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway
| العنوان: | Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway |
|---|---|
| المؤلفون: | Rui-Qing Jiao, Xiao-Juan Zhao, Lin-Lin Kang, Han-Wen Yu, Ling-Dong Kong, Yan-Zi Yang, Wen-Yuan Wu, Ke-Ke Jia, Tian-Yu Chen |
| المصدر: | Redox Biology, Vol 18, Iss, Pp 124-137 (2018) Redox Biology |
| بيانات النشر: | Elsevier BV, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Clinical Biochemistry, Peroxisome proliferator-activated receptor, PPAR-α, peroxisome proliferator activated receptor-α, medicine.disease_cause, Nrf2, nuclear factor erythroid 2-related factor 2, TNF-α, tumor necrosis factor-α, Biochemistry, GST, glutathione S-transferase, 0302 clinical medicine, HO-1, hemeoxygenase-1, lcsh:QH301-705.5, NAC, N-acetyl-L-cysteine, chemistry.chemical_classification, lcsh:R5-920, TXNIP, thioredoxin-interacting protein, Inflammasome, Transfection, SCD-1, stearoyl-CoA desaturase-1, Cell biology, Keap1, Kelch-like ECH-associated protein 1, H2O2, hydrogen peroxide, 030220 oncology & carcinogenesis, Signal transduction, medicine.symptom, lcsh:Medicine (General), TXNIP, Research Paper, ASC, apoptosis-associated speck-like protein, medicine.drug, miR-200a, microRNA-200a, NAFLD, non-alcoholic fatty liver disease, Excess fructose intake, Liver inflammation and lipid deposition, NLRP3, the NOD-like receptor (NLR) family, pyrin domain containing 3, tBHQ, tert-butylhydroquinone, Inflammation, 03 medical and health sciences, ROS, reactive oxygen species, MiR-200a, medicine, NQO1, NAD(P)H, quinone oxidoreductase 1, Keap1/Nrf2 pathway, MDA, malondialdehyde, Polydatin, Organic Chemistry, SREBP-1, sterol regulatory element binging protein 1, CPT-1, carnitine palmitoyl transferase-1, KEAP1, IL, interleukin, 030104 developmental biology, lcsh:Biology (General), chemistry, Oxidative stress |
| الوصف: | Oxidative stress is a critical factor in nonalcoholic fatty liver disease pathogenesis. MicroRNA-200a (miR-200a) is reported to target Kelch-like ECH-associated protein 1 (Keap1), which regulates nuclear factor erythroid 2-related factor 2 (Nrf2) anti-oxidant pathway. Polydatin (3,4′,5-trihydroxy-stilbene-3-β-D-glucoside), a polyphenol found in the rhizome of Polygonum cuspidatum, have anti-oxidative, anti-inflammatory and anti-hyperlipidemic effects. However, whether miR-200a controls Keap1/Nrf2 pathway in fructose-induced liver inflammation and lipid deposition and the blockade of polydatin are still not clear. Here, we detected miR-200a down-regulation, Keap1 up-regulation, Nrf2 antioxidant pathway inactivation, ROS-driven thioredoxin-interacting protein (TXNIP) over-expression, NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome activation and dysregulation of peroxisome proliferator activated receptor-α (PPAR-α), carnitine palmitoyl transferase-1 (CPT-1), sterol regulatory element binging protein 1 (SREBP-1) and stearoyl-CoA desaturase-1 (SCD-1) in rat livers, BRL-3A and HepG2 cells under high fructose induction. Furthermore, the data from the treatment or transfection of miR-200a minic, Keap1 and TXNIP siRNA, Nrf2 activator and ROS inhibitor demonstrated that fructose-induced miR-200a low-expression increased Keap1 to block Nrf2 antioxidant pathway, and then enhanced ROS-driven TXNIP to activate NLRP3 inflammasome and disturb lipid metabolism-related proteins, causing inflammation and lipid deposition in BRL-3A cells. We also found that polydatin up-regulated miR-200a to inhibit Keap1 and activate Nrf2 antioxidant pathway, resulting in attenuation of these disturbances in these animal and cell models. These findings provide a novel pathological mechanism of fructose-induced redox status imbalance and suggest that the enhancement of miR-200a to control Keap1/Nrf2 pathway by polydatin is a therapeutic strategy for fructose-associated liver inflammation and lipid deposition. Graphical abstract fx1 Highlights • Fructose decreases miR-200a expression to impair Keap1/Nrf2 pathway in NAFLD. • MiR-200a-driven oxidative stress is a causer in fructose-induced NAFLD. • Polydatin elevates miR-200a to regulate Keap1/Nrf2 pathway in fructose-induced NAFLD. • Polydatin lowers fructose-caused oxidative stress, inflammation and lipid deposition. • Enhancement of miR-200a expression by polydatin is a therapeutic strategy for NAFLD. |
| تدمد: | 2213-2317 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::483b832538db0d06f516c7947b302ae8Test https://doi.org/10.1016/j.redox.2018.07.002Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....483b832538db0d06f516c7947b302ae8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
|---|