CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice. Issue 2 (February 2017)

• Record Type: Journal Article
• Authors: Canup, Brandon S.B.; Song, Heliang; Le Ngo, Vu; Meng, Xiangxiao; Denning, Timothy L.; Garg, Pallavi; Laroui, Hamed
• Is Part Of: Digestive and liver disease. Volume 49:Issue 2(2017)
• Page Start: 188
• Page End: 196
• Publication Date: 2017-02
• Subjects: Hepatic CD98 -- Nonalcoholic fatty liver -- siRNA-loaded nanoparticles -- Targeted therapeutic strategy; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2016.11.008
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract: 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.