生命科学家在基因领域的“新大陆”——微小RNA(miRNA)领域,又有了惊喜发现:原本以为miRNA家族只是每个细胞“自产自用”的私家员工,没想到它们竟可以从“生产地”出发,跑遍生命体,执行“全球任务”,而且作用比传统的激素、细胞因子等信号蛋白更加高效、强劲,其能力效率堪比特工。这一发现使人类管窥到了一张全新的、巨大的生命调控网络。
以前,科学家一直认为miRNA是一类喜欢“宅”的分子,从“出生”起,一辈子就在一个细胞中活动。可是,南京大学生命科学院教授张辰宇的团队,却发现了这个家族极不平凡的一面。在研究一种编号为miRNA150的微小RNA时,他们发现免疫系统中的巨噬细胞在受到某种刺激后,会增加制造出miRNA150,并释放到循环的血液里,这“小个子”又会顺血流钻入内皮细胞中,刺激内皮细胞迁移。“血管内壁的内皮细胞一旦增殖与迁移增加,脂肪斑块就非常容易附着上去,最终形成血栓。”张辰宇说,这是动脉粥样硬化形成的重要原因之一,“如果发生在心脏中的冠状动脉中,就是我们所熟悉的冠心病。”
这一发现显然又为人类治疗这类疾病提供了一个新的机制与潜在的治疗靶点,但发现miRNA的新特点,意义更为重大。张辰宇告诉记者,通过进一步研究,他们发现miRNA与一般的激素分子、蛋白质不同,它似乎捧有“尚方宝剑”,能直接对基因“下令”,而不是通过冗长而复杂的信号传递去影响基因活动。更令人惊讶的是,一旦受到某种刺激,细胞会产生许多不同的miRNA,组成“特遣队”,被“派遣”到相应的靶细胞里,多管齐下,共同完成相同目的的调控任务。
这些成果已发表在7月9日出版的著名学术期刊《分子细胞》上。(生物谷Bioon.net)
生物谷推荐原文出处:
Molecular Cell DOI:10.1016/j.molcel.2010.06.010
Secreted Monocytic miR-150 Enhances Targeted Endothelial Cell Migration
Yujing Zhang, Danqing Liu, Xi Chen, Jing Li, Limin Li, Zhen Bian, Fei Sun, Jiuwei Lu, Yuan Yin, Xing Cai, Qi Sun, Kehui Wang, Yi Ba, Qiang Wang, Dongjin Wang, Junwei Yang, Pingsheng Liu, Tao Xu, Qiao Yan, Junfeng Zhang, Ke Zen, Chen-Yu Zhang
MicroRNAs (miRNAs) are a class of noncoding RNAs that regulate target gene expression at the posttranscriptional level. Here, we report that secreted miRNAs can serve as signaling molecules mediating intercellular communication. In human blood cells and cultured THP-1 cells, miR-150 was selectively packaged into microvesicles (MVs) and actively secreted. THP-1-derived MVs can enter and deliver miR-150 into human HMEC-1 cells, and elevated exogenous miR-150 effectively reduced c-Myb expression and enhanced cell migration in HMEC-1 cells. In vivo studies confirmed that intravenous injection of THP-1 MVs significantly increased the level of miR-150 in mouse blood vessels. MVs isolated from the plasma of patients with atherosclerosis contained higher levels of miR-150, and they more effectively promoted HMEC-1 cell migration than MVs from healthy donors. These results demonstrate that cells can secrete miRNAs and deliver them into recipient cells where the exogenous miRNAs can regulate target gene expression and recipient cell function.