近日，国际学术期刊Circulation Research在线发表了中科院上海生科院/上海交大医学院健康所核酸与分子医学研究组的最新研究进展：Two Functional MicroRNA-126s Repress a Novel Target Gene P21-Activated Kinase1 to Regulate Vascular Integrity in Zebrafish。
血管发育是胚胎发育的重要过程，研究血管发育的分子机制有重要的生理和病理意义。microRNA-126是内皮细胞特异表达的微小RNA(miRNA)，参与调节血管生成和维持血管完整性，但其具体作用机制尚待进一步阐明。
健康科学研究所博士生邹俊和李文庆等在荆清研究员的指导下，并与研究所刘廷析研究员课题组合作，利用斑马鱼作为模式生物，发现在斑马鱼基因组内存在两个miR-126位点（miR-126a/b），可在体外和体内产生成熟有生物活性的miRNA。研究发现miR-126a/b参与调节胚胎血管完整性，且有协同效应。进一步研究表明，miR-126a/b通过调节内皮细胞中pak1的表达水平达到调节血管完整性目的。该研究拓宽了对内皮细胞miRNA功能的认识，有助于阐明miRNA调节血管发育的作用机制和深入探索结构性血管疾病的发病机理。
该项研究工作得到了国家科技部、国家自然基金委、中国科学院的经费支持。（生物谷Bioon.com）
生物谷推荐原文出处：
Circulation Research doi: 10.1161/CIRCRESAHA.110.225045
Two Functional MicroRNA-126s Repress a Novel Target Gene p21-Activated Kinase 1 to Regulate Vascular Integrity in Zebrafish
Jun Zou ; Wen-Qing Li ; Qing Li ; Xiang-Qi Li ; Jun-Tao Zhang ; Gan-Qiang Liu ; Jian Chen ; Xiao-Xu Qiu ; Fu-Ju Tian ; Zhi-Zhang Wang ; Ni Zhu ; Yong-Wen Qin ; Bairong Shen ; Ting Xi Liu *; and Qing Jing *
Rationale: MicroRNAs (miRNAs) are key regulators of vascular development and diseases. The function and underlying mechanism of endothelial miRNAs have not been fully defined.
Objective: To investigate the role of endothelial miR-126 in zebrafish vascular development.
Methods and Results: Two homologs of miR-126, miR-126a (namely miR-126 in previous literature) and miR-126b, with only 1 nucleotide difference in their mature sequences, were identified in zebrafish genome. In vitro analysis showed that both precursors could sufficiently produce mature functional miRNAs. Expression analyses by Northern blot and quantitative RT-PCR showed that both miR-126s accumulated significantly 12 hours after fertilization and were specifically expressed in endothelial cells of zebrafish. Inhibition of miR-126a or miR-126b with specific morpholinos caused cranial hemorrhage, and simultaneous inhibition of both miR-126s resulted in a pronounced hemorrhage in higher percentage of embryos. Bioinformatics prediction showed that the targets of miR-126a/b partially overlapped but essentially differed. p21-activated kinase1 (pak1) was identified as a novel target of miR-126a/b, and pak1 3' untranslated region was differently regulated by these 2 miRNAs. Quantitative RT-PCR, in situ hybridization, and Western blot analyses showed that the level of pak1 was reduced when miR-126a/b were overexpressed. Notably, pak1 expression in endothelial cells was increased when miR-126a/b were knocked down. Furthermore, overexpression of the active form of human pak1 caused cranial hemorrhage, and knockdown pak1 effectively rescued the hemorrhage caused by inhibiting miR-126a/b.
Conclusions: Two functional endothelial cell–specific miRNAs, miR-126a and miR-126b, synergistically regulate zebrafish vascular integrity, and pak1 is a critical target of miR-126a/b in vascular development.
Key words: miR-126 ? pak1 ? vascular development ? zebrafish
