title: Enhanced apoptosis and senescence of bone-marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus.
abstract: Previous studies indicated that bone marrow mesenchymal stem cells (BMSCs) from patients with systemic lupus erythematosus (SLE) exhibited impaired capacities of proliferation, differentiation, secretion of cytokines, and immune modulation. In this study, we aimed to investigate whether apoptosis and senescence of SLE BMSCs were dysregulated. We found that there were increased frequencies of apoptotic and aging SLE BMSCs in comparison with those of normal controls. Notably, levels of Bcl-2 expression in SLE BMSCs were markedly decreased both at mRNA and protein levels. When BMSCs were induced to apoptosis by tumor necrosis factor-α (TNF-α) stimulation in vitro, the Bax and caspase 8 expression in SLE BMSCs was significantly increased at mRNA levels. The activity of caspase 8 was also enhanced in SLE BMSCs. More cytochrome-C-positive pellets in the cytosolic fraction of BMSCs were detected in SLE patients than in normal controls. The expression of Fas and tumor necrosis factor-α receptor 1 in SLE BMSCs was significantly upregulated compared with normal controls, and the serum levels of FasL and TNF-α were also elevated. Moreover, intracellular reactive oxygen species levels of SLE BMSCs were higher than those of normal controls, with the activation of PI3K/AKT/FoxO3 signaling pathway. Taken together, our results demonstrate increased apoptosis and senescence in SLE BMSCs, which may be associated with the pathogenesis of SLE.
authors.affiliation: Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Defang
authors.initials: D
authors.lastname: Meng
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Jiyun
authors.initials: J
authors.lastname: Zhang
authors.forename: Dongyan
authors.initials: D
authors.lastname: Shi
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.forename: Huji
authors.initials: H
authors.lastname: Xu
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000328:Adult; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000378:metabolism; D016922:Cellular Senescence; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000494:pharmacology; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C491901:FAS protein, human; C505661:FASLG protein, human; C499517:FOXO3 protein, human; D053222:Fas Ligand Protein; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8