近日,，國(guó)際學(xué)術(shù)期刊Circulation Research在線發(fā)表了中科院上海生科院/上海交大醫(yī)學(xué)院健康所核酸與分子醫(yī)學(xué)研究組的最新研究進(jìn)展：Two Functional MicroRNA-126s Repress a Novel Target Gene P21-Activated Kinase1 to Regulate Vascular Integrity in Zebrafish,。
血管發(fā)育是胚胎發(fā)育的重要過(guò)程,，研究血管發(fā)育的分子機(jī)制有重要的生理和病理意義。microRNA-126是內(nèi)皮細(xì)胞特異表達(dá)的微小RNA(miRNA),，參與調(diào)節(jié)血管生成和維持血管完整性，但其具體作用機(jī)制尚待進(jìn)一步闡明。
健康科學(xué)研究所博士生鄒俊和李文慶等在荊清研究員的指導(dǎo)下，并與研究所劉廷析研究員課題組合作,，利用斑馬魚作為模式生物,，發(fā)現(xiàn)在斑馬魚基因組內(nèi)存在兩個(gè)miR-126位點(diǎn)（miR-126a/b）,，可在體外和體內(nèi)產(chǎn)生成熟有生物活性的miRNA,。研究發(fā)現(xiàn)miR-126a/b參與調(diào)節(jié)胚胎血管完整性,，且有協(xié)同效應(yīng)。進(jìn)一步研究表明,，miR-126a/b通過(guò)調(diào)節(jié)內(nèi)皮細(xì)胞中pak1的表達(dá)水平達(dá)到調(diào)節(jié)血管完整性目的。該研究拓寬了對(duì)內(nèi)皮細(xì)胞miRNA功能的認(rèn)識(shí),，有助于闡明miRNA調(diào)節(jié)血管發(fā)育的作用機(jī)制和深入探索結(jié)構(gòu)性血管疾病的發(fā)病機(jī)理,。
該項(xiàng)研究工作得到了國(guó)家科技部,、國(guó)家自然基金委、中國(guó)科學(xué)院的經(jīng)費(fèi)支持,。（生物谷Bioon.com）
生物谷推薦原文出處：
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
