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学科主题: 临床医学
题名:
CD4 T-cell transcriptome analysis reveals aberrant regulation of STAT3 and Wnt signaling pathways in rheumatoid arthritis: evidence from a case-control study
作者: Ye, Hua1; Zhang, Jing1; Wang, Jun2; Gao, Yanyan1; Du, Yan1; Li, Chun1; Deng, Minghua2; Guo, Jianping1; Li, Zhanguo1
刊名: ARTHRITIS RESEARCH & THERAPY
发表日期: 2015-03-22
DOI: 10.1186/s13075-015-0590-9
卷: 17
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Rheumatology
研究领域[WOS]: Rheumatology
关键词[WOS]: HUMAN TH17 DIFFERENTIATION ; GENE ; PROTEIN ; NOTCH ; DESTRUCTION ; ACTIVATION ; SIGNATURES ; NETWORKS ; DISEASE ; GENOME
英文摘要:

Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease in which T cells play a pivotal role in the pathogenesis. Knowledge in terms of the CD4 T-cell transcriptome in RA is limited. The aim of this study was to examine the whole-genome transcription profile of CD4 T cells in RA by comparing patients with RA to healthy controls.

Methods: Peripheral blood CD4 T cells were isolated from 53 RA patients with active disease and 45 healthy individuals; 13 cases and 10 controls were enrolled in microarray analysis. The remaining 40 cases and 35 controls were recruited as an independent cohort for the validation study. Bioinformatics was performed on Gene Ontology (GO), gene-gene interaction networks, and pathway analysis. The gene modules, by combining the results from GO, gene networks, and pathway analysis, were selected for further validation.

Results: The CD4 T cells showed 1,496 differentially expressed (DE) genes in RA patients relative to healthy individuals. GO analysis revealed that the DE genes were enriched in immune response, T-cell response, apoptosis process, and Wnt receptor signaling. Pathway analysis also identified that ′Wnt signaling pathway′ was differentially regulated between two groups (P = 2.78 x 10(-10)). By gene-gene network analysis, we found that the DE genes were enriched in T-cell receptor (TCR), JAK-STAT signaling, and Wnt signaling pathway. By gene module analysis, we found that a number of DE genes overlapped in the three different analyses. In total, 23 genes were selected for further validation, and nine genes were confirmed. Of these, four genes (SOCS3, CBL, IFNAR1, and PIK3CA) were involved in STAT3 (signal transducer and activator of transcription 3) signaling, and three genes (CBL, KLF9, and CSNK2A1) were involved in the Wnt signaling pathway. Additionally, several zinc finger transcription factors (ZEB1, ZNF292, and ZNF644) were confirmed.

Conclusions: We report here the first case-control study of the CD4 T-cell transcriptome profile in RA. Our data provide evidence that CD4 T cells from patients with RA have abnormal functional networks in STAT3 signaling and Wnt signaling. Our results also suggest that the aberrant expression of several zinc finger transcription factors (ZEB1, ZNF292, and ZNF644) may be potential pathogenic factors for RA.

语种: 英语
所属项目编号: 2010CB529105 ; 81120108020 ; 31170840 ; 31270914 ; 7122192 ; 7122196 ; JWSL431
项目资助者: National Basic Research Program of China (Program 973) ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Peking University &prime ; Project 985&prime ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
WOS记录号: WOS:000352611500001
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65597
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China
2.Peking Univ, Ctr Quantitat Biol, Sch Math Sci, Beijing 100871, Peoples R China

Recommended Citation:
Ye, Hua,Zhang, Jing,Wang, Jun,et al. CD4 T-cell transcriptome analysis reveals aberrant regulation of STAT3 and Wnt signaling pathways in rheumatoid arthritis: evidence from a case-control study[J]. ARTHRITIS RESEARCH & THERAPY,2015,17.
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