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DOI | 10.1038/ncomms15003 |
Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes | |
Dieguez-Hurtado, Rodrigo1,2; Kato, Katsuhiro1; Giaimo, Benedetto Daniele3; Nieminen-Kelhae, Melina4,5; Arf, Hendrik1; Ferrante, Francesca3; Bartkuhn, Marek6; Zimmermann, Tobias7; Bixel, M. Gabriele1; Eilken, Hanna M.1,8; Adams, Susanne1; Borggrefe, Tilman3; Vajkoczy, Peter4,5; Adams, Ralf H.1,2 | |
2019-06-27 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany |
英文摘要 | Sufficient vascular supply is indispensable for brain development and function, whereas dysfunctional blood vessels are associated with human diseases such as vascular malformations, stroke or neurodegeneration. Pericytes are capillary-associated mesenchymal cells that limit vascular permeability and protect the brain by preserving blood-brain barrier integrity. Loss of pericytes has been linked to neurodegenerative changes in genetically modified mice. Here, we report that postnatal inactivation of the Rbpj gene, encoding the transcription factor RBPJ, leads to alteration of cell identity markers in brain pericytes, increases local TGF beta signalling, and triggers profound changes in endothelial behaviour. These changes, which are not mimicked by pericyte ablation, imperil vascular stability and induce the acquisition of pathological landmarks associated with cerebral cavernous malformations. In adult mice, loss of Rbpj results in bigger stroke lesions upon ischemic insult. We propose that brain pericytes can acquire deleterious properties that actively enhance vascular lesion formation and promote pathogenic processes. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000473002500006 |
WOS关键词 | CEREBRAL-BLOOD-FLOW ; IN-VIVO ; BETA ; ANGIOGENESIS ; PROGRESSION ; BINDING ; CONTRIBUTES ; DYSFUNCTION ; ACTIVATION ; PHENOTYPE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203264 |
专题 | 资源环境科学 |
作者单位 | 1.Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, Rontgenstr 20, D-48149 Munster, Germany; 2.Univ Munster, Fac Med, D-48149 Munster, Germany; 3.Univ Giessen, Inst Biochem, Friedrichstr 24, D-35392 Giessen, Germany; 4.Charite, Dept Neurosurg, Charitepl 1, D-10117 Berlin, Germany; 5.Berlin Inst Hlth, Charitepl 1, D-10117 Berlin, Germany; 6.Univ Giessen, Inst Genet, Heinrich Buff Ring 58-62, D-35392 Giessen, Germany; 7.Univ Giessen, Bioinformat & Syst Biol, Heinrich Buff Ring 58-62, D-35392 Giessen, Germany; 8.Bayer AG, Aprather Weg 18a, D-42113 Wuppertal, Germany |
推荐引用方式 GB/T 7714 | Dieguez-Hurtado, Rodrigo,Kato, Katsuhiro,Giaimo, Benedetto Daniele,et al. Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Dieguez-Hurtado, Rodrigo.,Kato, Katsuhiro.,Giaimo, Benedetto Daniele.,Nieminen-Kelhae, Melina.,Arf, Hendrik.,...&Adams, Ralf H..(2019).Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes.NATURE COMMUNICATIONS,10. |
MLA | Dieguez-Hurtado, Rodrigo,et al."Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes".NATURE COMMUNICATIONS 10(2019). |
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