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脂肪酸结合蛋白11a是斑马鱼脑血管完整性所必需的。

Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in Zebrafish.

作者信息

Zhang Jie, Qi Jialing, Wu Shuilong, Peng Lijiao, Shi Yunwei, Yang Jinxian, Yin Zhenhua, Gao Yu, Wang Chengniu, Gong Jie, Zhang Haijun, Zhang Jingjing, Liu Dong

机构信息

Medical School of Nantong UniversityNantong, China.

Affiliated Hospital of Guangdong Medical UniversityZhanjiang, China.

出版信息

Front Physiol. 2017 Apr 11;8:214. doi: 10.3389/fphys.2017.00214. eCollection 2017.

Abstract

The monolayer of endothelial cells (ECs) lining the intima of all blood vessel wall forms a semipermeable barrier that regulates tissue-fluid homeostasis, transport of nutrients, and migration of blood cells across the barrier. A number of signaling pathways and molecules mediate endothelial permeability, which plays important roles in a variety of the physiological and pathological conditions. Fatty acid binding proteins (FABPs) are able to bind various hydrophobic molecules, such as long-chain fatty acids, prostaglandins and eicosanoids. FABP4, a member of the family of FABPs, plays an important role in maintenance of glucose and lipid homeostasis as well as angiogenesis. In the present study, we found that , the ortholog of mammalian FABP4, was highly expressed in developing brain vessels of zebrafish. Knockout of gene caused hemorrhage in zebrafish brain. Morpholino mediated gene knockdown phenocopied the hemorrhage in mutants. Furthermore, we demonstrated permeability of brain vessels in mutant is significantly higher than that of control. In addition, COX and LOX inhibition partially rescued the brain vessel integrity defects caused by loss-of-function, suggesting the integrity defect was relevant to the Fatty Acid function.

摘要

所有血管壁内膜的单层内皮细胞(ECs)形成了一个半透屏障,该屏障调节组织液稳态、营养物质运输以及血细胞跨屏障迁移。许多信号通路和分子介导内皮通透性,其在多种生理和病理状况中发挥重要作用。脂肪酸结合蛋白(FABPs)能够结合各种疏水分子,如长链脂肪酸、前列腺素和类花生酸。FABP4是FABPs家族的一员,在维持葡萄糖和脂质稳态以及血管生成中发挥重要作用。在本研究中,我们发现,哺乳动物FABP4的直系同源物,在斑马鱼发育中的脑血管中高度表达。敲除该基因导致斑马鱼脑部出血。吗啉代介导的该基因敲低模拟了突变体中的出血现象。此外,我们证明该突变体中脑血管的通透性显著高于对照组。另外,COX和LOX抑制部分挽救了由该功能丧失导致的脑血管完整性缺陷,表明完整性缺陷与脂肪酸功能相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/128d/5387095/184a8fdeca34/fphys-08-00214-g0001.jpg

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