CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice

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• 作者：Brandon S.B. Canup^a ; Heliang Song^a ; Vu Le Ngo^b ; Xiangxiao Meng^a ; Timothy L. Denning^b ; Pallavi Garg^b ; Hamed Laroui^a ; ^b ; ^{hlaroui@gsu.edu}
• 关键词：Hepatic CD98 ; Nonalcoholic fatty liver ; siRNA-loaded nanoparticles ; Targeted therapeutic strategy
• 刊名：Digestive and Liver Disease
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：49
• 期：2
• 页码：188-196
• 全文大小：2815 K
• 卷排序：49

文摘

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.