紅細(xì)胞是人類和其它脊椎動(dòng)物血液中一種重要的細(xì)胞,，過(guò)多或過(guò)少都會(huì)引發(fā)嚴(yán)重的疾病,，但關(guān)于其數(shù)量變化機(jī)制一直以來(lái)卻并沒(méi)有明確的解釋,。美國(guó)德克薩斯大學(xué)西南醫(yī)學(xué)中心的一項(xiàng)研究或許能改變這一現(xiàn)狀，為貧血及紅細(xì)胞增多癥患者帶來(lái)福音,。相關(guān)研究發(fā)表在近日出版的《基因與發(fā)育》雜志上,。
在動(dòng)物實(shí)驗(yàn)中研究人員發(fā)現(xiàn)了一種能在紅細(xì)胞生成中起關(guān)鍵作用的微RNA。負(fù)責(zé)該項(xiàng)研究的德克薩斯大學(xué)西南醫(yī)學(xué)中心主任埃里克·奧爾森稱其是一種“功能強(qiáng)大的紅細(xì)胞產(chǎn)量調(diào)節(jié)器”,。因?yàn)閷?duì)這種名為miR-451的微RNA的抑制就可直接減少紅細(xì)胞的數(shù)量,。
紅細(xì)胞在骨髓中由干細(xì)胞形成，主要負(fù)責(zé)在身體中運(yùn)輸氧,，二氧化碳,，電解質(zhì)，葡萄糖以及氨基酸,，是脊椎動(dòng)物血液中數(shù)量最多的一種血細(xì)胞,。血液中的紅細(xì)胞過(guò)少將造成貧血，而過(guò)多又會(huì)導(dǎo)致中風(fēng)或血栓,。
論文的第一作者大衛(wèi)·帕特里克說(shuō)：“此前,，人們都知道m(xù)iR-451在成熟的紅細(xì)胞內(nèi)大量存在,，但其作用卻一概不知。”新研究中,，科學(xué)家通過(guò)轉(zhuǎn)基因技術(shù)培育了一只存在miR-451先天缺陷的小鼠,，結(jié)果發(fā)現(xiàn)該小鼠血液中的紅細(xì)胞數(shù)量極低，也難以通過(guò)常規(guī)方式產(chǎn)生更多的紅細(xì)胞,。
進(jìn)一步的研究中,，研究人員發(fā)現(xiàn)miR-451主要通過(guò)與其他RNA生成一種名為14-3-3-zeta的蛋白來(lái)實(shí)現(xiàn)這一過(guò)程，這種蛋白在多種細(xì)胞的成熟過(guò)程中都發(fā)揮著關(guān)鍵作用,。該研究小組同時(shí)也通過(guò)血液干細(xì)胞和人工合成RNA實(shí)現(xiàn)了對(duì)miR-451的抑制,，結(jié)果發(fā)現(xiàn)，紅細(xì)胞的數(shù)量同樣出現(xiàn)顯著減少,。
研究人員稱,，如果在臨床試驗(yàn)上這種干預(yù)也能成功，將意味著包括某些癌癥和真性紅細(xì)胞增多癥在內(nèi)的以紅細(xì)胞數(shù)及容量顯著增多為特點(diǎn)疾病將有望得到治愈,；與此同時(shí),，用該法制成增加紅細(xì)胞產(chǎn)量的藥物也將有助于貧血以及高原病的治療,。接下來(lái),，奧爾森和他的同事還將就miR-451抑制劑的作用，以及基于微RNA的藥物對(duì)其他血液類疾病的療效進(jìn)行進(jìn)一步的驗(yàn)證,。（生物谷Bioon.com）
生物谷推薦原文出處：
Genes & Development doi:10.1101/gad.1942810
Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3ζ
David M. Patrick, Cheng C. Zhang, Ye Tao, Huiyu Yao, Xiaoxia Qi, Robert J. Schwartz, Lily Jun-Shen Huang, and Eric N. Olson
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
2Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
3Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
4Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, USA;
5Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
6Texas Heart Institute, Texas Medical Center, Houston, Texas 77030, USA;
7Department of Biology and Biochemistry, The University of Houston, Houston, Texas 77004, USA
Erythrocyte formation occurs throughout life in response to cytokine signaling. We show that microRNA-451 (miR-451) regulates erythropoiesis in vivo. Mice lacking miR-451 display a reduction in hematrocrit, an erythroid differentiation defect, and ineffective erythropoiesis in response to oxidative stress. 14-3-3ζ, an intracellular regulator of cytokine signaling that is repressed by miR-451, is up-regulated in miR-451?/? erythroblasts, and inhibition of 14-3-3ζ rescues their differentiation defect. These findings reveal an essential role of 14-3-3ζ as a mediator of the proerythroid differentiation actions of miR-451, and highlight the therapeutic potential of miR-451 inhibitors.
