title: CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice.
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.
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors.forename: Brandon S B
authors.initials: BS
authors.lastname: Canup
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors.forename: Heliang
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors.forename: Vu
authors.initials: V
authors.lastname: Le Ngo
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors.forename: Xiangxiao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Denning
authors.affiliation: Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Garg
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA; Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA. Electronic address: hlaroui@gsu.edu.
authors.forename: Hamed
authors.initials: H
authors.lastname: Laroui
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D027261:Fusion Regulatory Protein-1 / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D065626:Non-alcoholic Fatty Liver Disease / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D015415:Biomarkers; D027261:Fusion Regulatory Protein-1; D034741:RNA, Small Interfering
keywords: Hepatic CD98; Nonalcoholic fatty liver; Targeted therapeutic strategy; siRNA-loaded nanoparticles