摘要
背景:血脑屏障(BBB)完整性的妥协常常与人类出血性中风和神经退行性疾病有关,包括视网膜病变,如老年性黄斑变性和糖尿病视网膜病变。脑细胞在血脑屏障完整性的监管和维护中发挥关键作用。然而,机制的脑细胞发展建立血脑屏障完整性仍不清楚。 方法:斑马鱼转基因株系的TG(Flk1:绿色荧光蛋白;基因:基因)、Tg(Flk1:GFP)、Tg(FLI1:GFP)和Tg(BRE:GFP)中使用了这项工作。研究牛的功能被吗啉代寡核苷酸(MO)进行注射,染料渗透法、RT-PCR、活体成像、免疫荧光染色及静力学分析。 结果:我们在这里报告,BMP3调节BBB的完整性,促进细胞的斑马鱼大脑发展。沉默与BMP3 MO BMP3导致脑出血在斑马鱼胚胎。同时,通过注射牛BMP3莫中断功能损害脑周细胞覆盖在斑马鱼胚胎。机械地,击倒BMP3破坏模式和BMP在斑马鱼的大脑信号的活动,从而可能破坏平衡的TGF-β在斑马鱼胚胎β/ BMP信号。 结论:综上所述,我们的数据表明,调节血脑屏障的完整性可能通过促进牛周发展。
关键词: 血脑屏障(BBB),BMP3,周细胞,渗透,出血,斑马鱼。
Current Molecular Medicine
Title:bmp3 is Required for Integrity of Blood Brain Barrier by Promoting Pericyte Coverage in Zebrafish Embryos
Volume: 17 Issue: 4
关键词: 血脑屏障(BBB),BMP3,周细胞,渗透,出血,斑马鱼。
摘要: Background: The compromise of blood brain barrier (BBB) integrity is often associated with human hemorrhage stroke and neurodegeneration diseases, including retina diseases, such as age-related macular degeneration and diabetic retinopathy. Brain pericytes play pivotal roles in regulation and maintenance of BBB integrity. However, the mechanisms underlying brain pericyte development to establish BBB integrity remain unclear.
Methods: Zebrafish transgenic lines Tg(flk1:GFP; gata1:dsRed), Tg(flk1:GFP), Tg(fli1:GFP) and Tg(BRE:GFP) were used in this work. The functional studies of bmp3 were performed by mopholino oligonucleotide (MO) injection, dye-based permeability assay, RT-PCR, in vivo imaging, immunofluorescence staining and statics analysis.
Results: Here we report that bmp3 regulates BBB integrity in zebrafish brain by promoting pericyte development. Knockdown of bmp3 with injection of bmp3-MO causes intracerebral hemorrhage in zebrafish embryos. Meanwhile, disruption of bmp3 function by bmp3-MO injection impairs cerebral pericyte coverage in zebrafish embryos. Mechanistically, knockdown of bmp3 disrupts the pattern and activities of BMP signaling in zebrafish brain, thus probably disrupting the balance of TGFβ/BMP signaling in zebrafish embryos.
Conclusion: In summary, our data shows that bmp3 regulates BBB integrity potentially by promoting pericyte development.
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Cite this article as:
bmp3 is Required for Integrity of Blood Brain Barrier by Promoting Pericyte Coverage in Zebrafish Embryos, Current Molecular Medicine 2017; 17 (4) . https://dx.doi.org/10.2174/1566524017666171106114234
DOI https://dx.doi.org/10.2174/1566524017666171106114234 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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