title: Down-regulation of nectin-4 inhibits apoptosis in systemic lupus erythematous (SLE) through targeting Bcl-2/Bax pathway.
abstract: OBJECTIVE
  The purpose of this study was to investigate the potential role of nectin-4 in systemic lupus erythematous (SLE) cell apoptosis during the disease development and its potential mechanism.
  
  
  METHODS
  Human peripheral blood mononuclear cells (PBMCs) were obtained for the isolation of monocytes and T lymphocytes. siRNA-nectin-4 plasma was constructed for the transfection into T cells using Lipofectamine 2000 reagent. siRNA with no nectin-4 sequence was transfected into T cells for the control group. mRNA expression of nectin-4 in cells was analyzed using RT-PCR method. Effect of netin-4 expression on T cell apoptosis was analyzed with Annexin V-FITC cell apoptosis kit. Moreover, effects of nectin-4 expression on cell apoptotic-related proteins expressions were detected using western blotting analysis.
  
  
  RESULTS
  Nectin-4 was significantly overexpressed in cells from SLE group compared with healthy control (HC) group (P<0.05). When T cells were transfected with sinectin-4, nectin-4 slicing increased cell apoptosis in HC group but significantly decreased apoptosis in SLE group (P<0.05). Nectin-4 slicing significantly decreased CD40L and CD17 expressions in SLE (P<0.05), but performed no effect on CD11a expression. Moreover, nectin-4 down-regulation could significantly decrease Bcl-2, Bcl-XL, and caspase-6 expressions but increase Bax level in SLE group.
  
  
  CONCLUSIONS
  The data presented in this study suggested that nectin-4 may be a therapeutic target for SLE through affecting the cell apoptosis.
authors.affiliation: Department of Nephrology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D000075983:Nectins
chemical_list: D015815:Cell Adhesion Molecules; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C442228:NECTIN4 protein, human; D000075983:Nectins
keywords: Bcl-2/Bax pathway; Systemic lupus erythematous (SLE); caspase; cell apoptosis; nectin-4