MicroRNA-155 Regulates ROS Production, NO Generation, Apoptosis and Multiple Functions of Human Brain Microvessel Endothelial Cells Under Physiological and Pathological Conditions
MicroRNA-155 Regulates ROS Production, NO Generation, Apoptosis and Multiple Functions of Human Brain Microvessel Endothelial Cells Under Physiological and Pathological Conditions
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MicroRNA-155在生理病理条件下调控人脑微血管内皮细胞ROS产生、NO产生、凋亡及多种功能
DOI：
10.1002/jcb.25234
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发表时间：
2015-12-01
影响因子：
4
通讯作者：
Ma, Xiaotang
中科院分区：
文献类型：
--
作者：
Liu, Yajing;Pan, Qunwen;Ma, Xiaotang
microRNA-155（miR 155）调节细胞的各种功能。内皮细胞（endothelial cells，ECs）的功能障碍或损伤在多种血管疾病的发病机制中起着重要作用。在这项研究中，我们研究了miR 155在生理和病理条件下在人脑微血管内皮细胞（HBMEC）中的作用和潜在机制。我们检测miR 155沉默对基础水平和氧化低密度脂蛋白（ox-LDL）诱导的HBMEC活性氧（ROS）生成、一氧化氮（NO）生成、凋亡和功能的影响。Western blot和q-PCR检测表皮生长因子受体（EGFR）、细胞外调节蛋白激酶（ERK）、p38丝裂原活化蛋白激酶（p38 MAPK）、磷脂酰肌醇-3-激酶（PI 3 K）、丝氨酸/苏氨酸激酶（Akt）、活化半胱氨酸蛋白酶-3（caspase-3）和细胞间粘附分子-1（ICAM-1）的基因表达。结果表明：（1）miR 155沉默可抑制HBMEC凋亡和活性氧（ROS）的产生，促进一氧化氮（NO）的产生。(2)miR 155沉默增加了HBMEC的增殖、迁移和管形成能力，同时降低了细胞粘附能力。(3)基因表达分析显示，miR 155敲低后，EGFR/ERK/p38 MAPK和PI 3 K/Akt表达增加，活化的caspase-3和ICAM-1 mRNA表达减少。结论：miR 155基因敲低可通过调控caspase-3、ICAM-1、EGFR/ERK/p38 MAPK和PI 3 K/Akt通路等多种基因的表达来调节HBMEC的ROS生成、NO生成、凋亡和功能。J.细胞。116：2870-2881，2015. (c)2015 Wiley Periodicals，Inc.
The microRNA-155 (miR155) regulates various functions of cells. Dysfunction or injury of endothelial cells (ECs) plays an important role in the pathogenesis of various vascular diseases. In this study, we investigated the role and potential mechanisms of miR155 in human brain microvessel endothelial cells (HBMECs) under physiological and pathological conditions. We detected the effects of miR155 silencing on ROS production, NO generation, apoptosis and functions of HBMECs at basal and in response to oxidized low density lipoprotein (ox-LDL). Western blot and q-PCR were used for analyzing the gene expression of epidermal growth factor receptor (EGFR)/extracellular regulated protein kinases (ERK)/p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositol-3-kinase (PI3K) and serine/threonine kinase(Akt), activated caspase-3, and intercellular adhesion molecule-1 (ICAM-1). Results showed that under both basal and challenge situations: (1) Silencing of miR155 decreased apoptosis and reactive oxygen species (ROS) production of HBMECs, whereas, promoted nitric oxide (NO) generation. (2) Silencing of miR155 increased the proliferation, migration, and tube formation ability of HBMECs, while decreased cell adhesion ability. (3) Gene expression analyses showed that EGFR/ERK/p38 MAPK and PI3K/Akt were increased and that activated caspase-3 and ICAM-1 mRNA were decreased after knockdown of miR155. In conclusion, knockdown of miR155 could modulate ROS production, NO generation, apoptosis and function of HBMECs via regulating diverse gene expression, such as caspase-3, ICAM-1 and EGFR/ERK/p38 MAPK and PI3K/Akt pathways. J. Cell. Biochem. 116: 2870-2881, 2015. (c) 2015 Wiley Periodicals, Inc.