期刊
DIGESTIVE AND LIVER DISEASE
卷 49, 期 2, 页码 188-196出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.dld.2016.11.008
关键词
Hepatic CD98; Nonalcoholic fatty liver; siRNA-loaded nanoparticles; Targeted therapeutic strategy
资金
- Chemistry Department
- Center for Diagnostics and Therapeutics of Georgia State University
- National Institutes of Health of Diabetes and Digestive and Kidney Diseases [K01-DK-097192]
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) could attenuate liver disease markers in a mouse model of NAFLD. NPs were generated using a double emulsion/solvent evaporation technique. Mice fed a high fat diet for 8 weeks to induce fatty liver were treated with vein tail injections of CD98 siRNA-loaded NPs. In vitro, HepG2 treated with CD98 siRNA-loaded NPs showed significant downregulation of CD98 leading to a significant decrease of major pro inflammatory cytokines and markers. In vivo, CD98 siRNA-loaded NPs strongly decreased all markers of NAFLD, including the blood levels of ALT and lipids accumulation, fibrosis evidence and pro-inflammatory cytokines. In conclusion, our results indicate that CD98 appears to function as a key actor/inducer in NAFLD, and that our NPs approach may offer a new targeted therapeutic for this disease. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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