Target validation in hypoxia-induced vascular remodeling using transcriptome/metabolome analysis
Target validation in hypoxia-induced vascular remodeling using transcriptome/metabolome analysis
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DOI：
10.1038/sj.tpj.6500177
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Tanaka, T
中科院分区：
文献类型：
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作者：
Amano, H;Maruyama, K;Tanaka, T
本研究描述了联合转录组和代谢组学分析，用于缺氧诱导的血管重塑的治疗靶点验证。暴露于缺氧条件下导致S100 C mRNA的上调和增加牛磺酸（2-氨基乙磺酸）在大鼠肺的含量，如所示的差异显示和氨基酸含量分析。缺氧通过缺氧诱导因子-1（HIF-1）激活S100 C启动子的转录。牛磺酸抑制HIF-1介导的S100 C转录增加。此外，口服牛磺酸管理衰减缺氧大鼠肺血管重塑，而内源性牛磺酸的管理β-丙氨酸的消耗导致血管重塑增加。通过牛磺酸抑制HIF转录可能在预防缺氧诱导的血管重塑中具有治疗益处。总之，我们使用转录组和代谢组分析来鉴定在缺氧诱导的血管重塑中起关键作用的治疗性低分子量配体。这些技术提供了一个很好的策略筛选和验证的目标。
The present study describes combined transcriptome and metabolome analysis for therapeutic target validation in hypoxia-induced vascular remodeling. Exposure to hypoxic conditions resulted in the upregulation of S100C mRNA and increased taurine (2-aminoethanesulfonic acid) content in the rat lung, as demonstrated by differential display and amino-acid content analysis. Hypoxia resulted in transcriptional activation of the S100C promoter through hypoxia-inducible factor-1 (HIF-1). Taurine suppressed HIF-1-mediated increases in S100C transcription. Moreover, oral taurine administration attenuated vascular remodeling in hypoxic rat lung, whereas depletion of endogenous taurine by administration of beta-alanine resulted in increased vascular remodeling. Inhibition of HIF transcription by taurine may be of therapeutic benefit in preventing hypoxia-induced vascular remodeling. In conclusion, we used transcriptome and metabolome analysis to identify a therapeutic low-molecular-weight ligand that plays a critical role in hypoxia-induced vascular remodeling. These techniques provided an excellent strategy for screening and validation of targets.