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基于等压标签定量法的博来霉素诱导肺纤维化的比较蛋白质组学分析

Comparative Proteomic Analysis of Bleomycin-induced Pulmonary Fibrosis Based on Isobaric Tag for Quantitation.

作者信息

Yang Tiejun, Jia Yanlong, Ma Yongkang, Cao Liang, Chen Xiaobing, Qiao Baoping

机构信息

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; Department of Urology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.

Pharmacy College, Xinxiang Medical University, Xinxiang, Henan, PR China.

出版信息

Am J Med Sci. 2017 Jan;353(1):49-58. doi: 10.1016/j.amjms.2016.11.021. Epub 2016 Nov 18.

DOI:10.1016/j.amjms.2016.11.021
PMID:28104103
Abstract

BACKGROUND

Pulmonary fibrosis (PF) is a destructive pulmonary disease and the molecular mechanisms underlying PF are unclear. This study investigated differentially expressed proteins associated with the occurrence and development of PF in rat lung tissue with bleomycin-induced PF.

METHODS

Sixteen Sprague-Dawley rats were randomly divided into 2 groups: the PF model group (n = 8) and the control group (n = 8). After successfully establishing the rat PF model induced by bleomycin, the differentially expressed proteins in the 2 groups were identified through isobaric tag for relative and absolute quantitation coupled with liquid chromatography-mass spectrometry and bioinformatics analysis.

RESULTS

A total of 146 differentially expressed proteins were identified; 88 of which displayed increased abundance and 58 were downregulated in the PF rat model group. Most functional proteins were associated with extracellular matrix, inflammation, damage response, vitamin A synthesis and metabolism. Critical proteins related to PF development and progression was identified, such as type V collagen-3, arachidonic acid 12-lipoxygenase, arachidonic acid 15-lipoxygenase and cytochrome P4501A1. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these differentially expressed proteins were enriched in extracellular matrix receptor interaction pathway, renin-angiotensin system and metabolic pathway of retinol.

CONCLUSIONS

The proteins expressed in bleomycin-induced PF rat model provide important data for further functional analysis of proteins involved in PF.

摘要

背景

肺纤维化(PF)是一种具有破坏性的肺部疾病,其潜在的分子机制尚不清楚。本研究调查了博来霉素诱导的PF大鼠肺组织中与PF发生发展相关的差异表达蛋白。

方法

将16只Sprague-Dawley大鼠随机分为2组:PF模型组(n = 8)和对照组(n = 8)。成功建立博来霉素诱导的大鼠PF模型后,通过相对和绝对定量的等压标签结合液相色谱-质谱联用及生物信息学分析,鉴定两组中的差异表达蛋白。

结果

共鉴定出146种差异表达蛋白;其中88种在PF大鼠模型组中丰度增加,58种下调。大多数功能蛋白与细胞外基质、炎症、损伤反应、维生素A合成和代谢有关。鉴定出与PF发生发展相关的关键蛋白,如V型胶原-3、花生四烯酸12-脂氧合酶、花生四烯酸15-脂氧合酶和细胞色素P4501A1。京都基因与基因组百科全书通路分析表明,这些差异表达蛋白在细胞外基质受体相互作用通路、肾素-血管紧张素系统和视黄醇代谢通路中富集。

结论

博来霉素诱导的PF大鼠模型中表达的蛋白为进一步对参与PF的蛋白进行功能分析提供了重要数据。

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