Bmp3通过促进斑马鱼胚胎中周细胞覆盖来维持血脑屏障的完整性。

bmp3 is Required for Integrity of Blood Brain Barrier by Promoting Pericyte Coverage in Zebrafish Embryos.

作者信息

Lei D, Jin X, Wen L, Dai H, Ye Z, Wang G

机构信息

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China.

出版信息

Curr Mol Med. 2017 Dec 7;17(4):298-303. doi: 10.2174/1566524017666171106114234.

DOI:10.2174/1566524017666171106114234

PMID:29110609

Abstract

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.

摘要

背景

血脑屏障（BBB）完整性受损常与人类出血性中风及神经退行性疾病相关，包括视网膜疾病，如年龄相关性黄斑变性和糖尿病性视网膜病变。脑周细胞在BBB完整性的调节和维持中起关键作用。然而，脑周细胞发育以建立BBB完整性的潜在机制仍不清楚。

方法

本研究使用了斑马鱼转基因品系Tg(flk1:GFP; gata1:dsRed)、Tg(flk1:GFP)、Tg(fli1:GFP)和Tg(BRE:GFP)。通过注射吗啉代寡核苷酸（MO）、基于染料的通透性测定、RT-PCR、体内成像、免疫荧光染色和统计学分析对bmp3进行功能研究。

结果

在此我们报告，bmp3通过促进周细胞发育来调节斑马鱼脑内的BBB完整性。注射bmp3-MO敲低bmp3会导致斑马鱼胚胎脑内出血。同时，注射bmp3-MO破坏bmp3功能会损害斑马鱼胚胎脑周细胞的覆盖。机制上，敲低bmp3会破坏斑马鱼脑中BMP信号的模式和活性，从而可能破坏斑马鱼胚胎中TGFβ/BMP信号的平衡。