title: High level of reactive oxygen species impaired mesenchymal stem cell migration via overpolymerization of F-actin cytoskeleton in systemic lupus erythematosus.
abstract: Some lines of evidence have demonstrated abnormalities of bone marrow mesenchymal stem cells (MSCs) in systemic lupus erythematosus (SLE) patients, characterized by defective phenotype of MSCs and slower growth with enhanced apoptosis and senescence. However, whether SLE MSCs demonstrate aberrant migration capacity or abnormalities in cytoskeleton are issues that remain poorly understood. In this study, we found that MSCs from SLE patients did show impairment in migration capacity as well as abnormalities in F-actin cytoskeleton, accompanied by a high level of intracellular reactive oxygen species (ROS). When normal MSCs were treated in vitro with H2O2, which increases intracellular ROS level as an oxidant, both reorganization of F-actin cytoskeleton and impairment of migration capability were observed. On the other hand, treatment with N-acetylcysteine (NAC), as an exogenous antioxidant, made F-actin more orderly and increased migration ratio in SLE MSCs. In addition, oral administration of NAC markedly reduced serum autoantibody levels and ameliorated lupus nephritis (LN) in MRL/lpr mice, partially reversing the abnormalities of MSCs. These results indicate that overpolymerization of F-actin cytoskeleton, which may be associated with high levels of ROS, causes impairment in the migration capacity of SLE MSCs and that oral administration of NAC may have potential therapeutic effects on MRL/lpr mice.
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, 210008 Nanjing, Jiangsu, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, 210008 Nanjing, Jiangsu, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, 210008 Nanjing, Jiangsu, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, 321, Zhongshan Road, 210008 Nanjing, Jiangsu, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Che
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, 210008 Nanjing, Jiangsu, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, 321, Zhongshan Road, 210008 Nanjing, Jiangsu, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, 1975, Zonal Avenue, CA 90089-9031 KAM B-16, Los Angeles, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, 210008 Nanjing, Jiangsu, PR China. Electronic address: lingyunsun@nju.edu.cn.
authors.forename: L
authors.initials: L
authors.lastname: Sun
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D055503:Protein Multimerization / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000199:Actins; D017382:Reactive Oxygen Species
keywords: Cellules souches mésenchymateuses; Dérivés réactifs de l’oxygène (DRO); F-actin; F-actine; Lupus érythémateux disséminé; MRL/lpr mice; Mesenchymal stem cells; Migration; N-acétylcystéine; NAC; Reactive oxygen species; Souris de lignée MRL/lpr; Systemic lupus erythematosus