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基于蛋白质-DNA阵列鉴定闭塞性细支气管炎中差异调节的转录因子活性

Protein-DNA array-based identification of transcription factor activities differentially regulated in obliterative bronchiolitis.

作者信息

Dong Ming, Wang Xin, Zhao Hong-Lin, Zhao Yu-Xia, Jing Ya-Qing, Yuan Jing-Hua, Guo Yi-Jiu, Chen Xing-Long, Li Ke-Qiu, Li Guang

机构信息

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital No. 154 Anshan Road, Tianjin 300052, PR China.

Department of Pediatric Surgery, Tianjin Children's Hospital No. 225 Race Course Road, Tianjin 300074, PR China.

出版信息

Int J Clin Exp Pathol. 2015 Jun 1;8(6):7140-8. eCollection 2015.

Abstract

Lung transplantation has already become the preferred treatment option for a variety of end-stage pulmonary failure. However the long-term results of lung transplantation are still not compelling and the major death reason is commonly due to obliterative bronchiolitis (OB) which is considered as chronic rejection presenting manifests physiologically as a progressive decline in FEV1. Transcription factors (TFs) play a key role in regulating gene expression and in providing an interconnecting regulatory between related pathway elements. Although the transcription factors are required for expression of the proinflammatory cytokines and immune proteins which are involved in obliterative bronchiolitis following lung transplantation, the alterations of the transcription factors in OB have not yet been revealed. Therefore, to investigate the alteration pattern of the transcription factors in OB, we used protein/DNA arrays. Mice orthotopic tracheal transplantation model was used in this studying. In this study, we explored the activity profiles of TFs in Protein/DNA array data of tracheal tissue in 14 and 28 day after transplanted. From a total of 345 screened TFs, we identified 42 TFs that showed associated with OB progression. Our data indicate that TFs may be potentially involved in the pathogenesis of OB, and can prevent, diagnose and treat OB after lung transplantation. In development of OB, some of the TFs may have ability to modulate the transcription of inflammatory proteins such cytokines, inflammatory enzymes and so on.

摘要

肺移植已成为各种终末期肺衰竭的首选治疗方案。然而,肺移植的长期效果仍不尽人意,主要死亡原因通常是闭塞性细支气管炎(OB),它被认为是慢性排斥反应,生理表现为第一秒用力呼气量(FEV1)逐渐下降。转录因子(TFs)在调节基因表达以及在相关通路元件之间提供相互连接的调节方面发挥着关键作用。尽管转录因子是肺移植后闭塞性细支气管炎中涉及的促炎细胞因子和免疫蛋白表达所必需的,但OB中转录因子的变化尚未被揭示。因此,为了研究OB中转录因子的变化模式,我们使用了蛋白质/DNA阵列。本研究采用小鼠原位气管移植模型。在这项研究中,我们在移植后14天和28天的气管组织蛋白质/DNA阵列数据中探索了转录因子的活性谱。从总共345个筛选出的转录因子中,我们鉴定出42个与OB进展相关的转录因子。我们的数据表明,转录因子可能潜在地参与了OB的发病机制,并可用于肺移植后OB的预防、诊断和治疗。在OB的发展过程中,一些转录因子可能具有调节炎症蛋白如细胞因子、炎症酶等转录的能力。

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