Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in Zebrafish.
Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in Zebrafish.
复制标题
斑马鱼脑血管完整性需要脂肪酸结合蛋白 11a
DOI：
10.3389/fphys.2017.00214
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发表时间：
2017
影响因子：
4
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Zhang J;Qi J;Wu S;Peng L;Shi Y;Yang J;Yin Z;Gao Y;Wang C;Gong J;Zhang H;Zhang J;Liu D
内皮细胞(ECs)的单层排列在所有血管壁的内膜上，形成一个半渗透屏障，调节组织液的动态平衡、营养物质的运输和血细胞的跨屏障迁移。许多信号通路和分子介导内皮细胞通透性，在多种生理和病理条件下发挥重要作用。脂肪酸结合蛋白(FABP)能结合多种疏水分子，如长链脂肪酸、前列腺素和二十烷类化合物。FABP4是FABP家族中的一员，在维持糖脂平衡和血管生成方面发挥着重要作用。在本研究中，我们发现哺乳动物FABP4的同源基因Fabp11a在斑马鱼发育中的脑血管中高表达。Fabp11a基因敲除导致斑马鱼大脑出血。吗啡介导的Fabp11a基因敲除突变体的出血现象。此外，我们还发现突变体的脑血管通透性显著高于对照。此外，COX和LOX抑制可部分挽救由Fabp11a功能丧失引起的脑血管完整性缺陷，提示该完整性缺陷与脂肪酸功能有关。
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 fabp11a, the ortholog of mammalian FABP4, was highly expressed in developing brain vessels of zebrafish. Knockout of fabp11a gene caused hemorrhage in zebrafish brain. Morpholino mediated fabp11a gene knockdown phenocopied the hemorrhage in mutants. Furthermore, we demonstrated permeability of brain vessels in fabp11a mutant is significantly higher than that of control. In addition, COX and LOX inhibition partially rescued the brain vessel integrity defects caused by fabp11a loss-of-function, suggesting the integrity defect was relevant to the Fatty Acid function.