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鉴定出一组在微血管中具有广泛且特异性表达的58个基因转录本的核心集。

Identification of a core set of 58 gene transcripts with broad and specific expression in the microvasculature.

作者信息

Wallgard Elisabet, Larsson Erik, He Liqun, Hellström Mats, Armulik Annika, Nisancioglu Maya H, Genove Guillem, Lindahl Per, Betsholtz Christer

机构信息

Department of Medical Biochemistry and Biophysics, KarolinskaInstitutet, Scheeles väg 2, A3, floor 4, SE-171 77, Stockholm, Sweden.

出版信息

Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1469-76. doi: 10.1161/ATVBAHA.108.165738. Epub 2008 May 15.

Abstract

OBJECTIVE

Pathological angiogenesis is an integral component of many diseases. Antiangiogenesis and vascular targeting are therefore promising new therapeutic principles. However, few endothelial-specific putative drug targets have been identified, and information is still limited about endothelial-specific molecular processes. Here we aimed at determining the endothelial cell-specific core transcriptome in vivo.

METHODS AND RESULTS

Analysis of publicly available microarray data identified a mixed vascular/lung cluster of 132 genes that correlated with known endothelial markers. Filtering against kidney glomerular/nonglomerular and brain vascular/nonvascular microarray profiles separated contaminating lung markers, leaving 58 genes with broad and specific microvascular expression. More than half of these have not previously been linked to endothelial functions or studied in detail before. The endothelial cell-specific expression of a selected subset of these, Eltd1, Gpr116, Ramp2, Slc9a3r2, Slc43a3, Rasip1, and NM_023516, was confirmed by real-time quantitative polymerase chain reaction and/or immunohistochemistry.

CONCLUSIONS

We have used a combination of publicly available and own microarray data to identify 58 gene transcripts with broad yet specific expression in microvascular endothelium. Most of these have unknown functions, but many of them are predicted to be cell surface expressed or implicated in cell signaling processes and should therefore be explored as putative microvascular drug targets.

摘要

目的

病理性血管生成是许多疾病的一个重要组成部分。因此,抗血管生成和血管靶向是很有前景的新治疗原则。然而,很少有内皮细胞特异性的假定药物靶点被确定,并且关于内皮细胞特异性分子过程的信息仍然有限。在这里,我们旨在确定体内内皮细胞特异性核心转录组。

方法与结果

对公开可用的微阵列数据进行分析,确定了一个由132个基因组成的混合血管/肺簇,这些基因与已知的内皮标记物相关。通过与肾小球/非肾小球以及脑血管/非血管微阵列图谱进行比对,筛选出污染性的肺标记物,留下58个具有广泛且特异性微血管表达的基因。其中超过一半的基因此前尚未与内皮功能相关联或进行过详细研究。通过实时定量聚合酶链反应和/或免疫组织化学证实了这些基因中选定子集(Eltd1、Gpr116、Ramp2、Slc9a3r2、Slc43a3、Rasip1和NM_023516)的内皮细胞特异性表达。

结论

我们结合公开可用数据和自身微阵列数据,确定了58个在微血管内皮中具有广泛且特异性表达的基因转录本。其中大多数功能未知,但它们中的许多预计在细胞表面表达或参与细胞信号传导过程,因此应作为假定的微血管药物靶点进行探索。

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