2018年孤儿核受体Nur77与肺部疾病.docVIP

孤儿核受体Nur77与肺部疾病 　　垦堕壁堡盘查!!!!至!!旦筮!!鲞筮!!塑 !坐』垦笪2111旦!!!里!!!!!!!!y!!:!!!堕!:!! 　　孤儿核受体Nur77与肺部疾病 　　张畅徐希 商艳李强 　　【摘要】Nur77作为NR4A孤儿核受体超家族的一员,可被多种激素、炎症反应和生长因子诱导表 达,具有复杂的生物学功能,参与细胞的增殖、分化和凋亡过程。其中值得注意的是Nur77可通过由细 胞核向细胞质移位介导一种新的细胞凋亡机制。大量研究表明Nur77与多种肺部疾病发病机制关系密 切,如呼吸机过度通气引发的肺部炎症性损伤,镉中毒诱发的肺组织细胞凋亡和肺动脉高压血管平滑肌 细胞增殖的负反馈调节机制等。此外,Nur77还与肺癌的发生发展有关,同时也参与维甲酸的抗肺癌机 制。因此,本文就Nur77及其与肺部疾病的关系作一综述。 　　【关键词1Nur77;呼吸机所致肺损伤;镉中毒致肺损伤;肺动脉高压;肺癌 　　Orphan nuclear receptor Nut77and pulmonary disease Zhang Chang,Xu Xi,Shang Yah,Li Qiang. Department of Respiratory Medicine,Changhai Hospital,the Second Military Medical University, Shanghai 200433,China 　　Corresponding author:Shang Yan,Email:s_Il口,zgy口行75j200@163.corn 　　[Abstract]Nur77,one of nuclear receptor 4A(NR4A)family members,is activated by many physiological stimuli including hormones,inflammation and growth factors,and involved in a variety of biological processes such as proliferation,differentiation,and apoptosis.Significantly,Nur77can induce a new kind of apoptotic mechanism by translocating from the nucleus to mitochondria.Accumulating evidences demonstrate that Nur77is associated with many pulmonary diseases,including ventilator-induced lung inflammatory injury,cadmium—induced apoptosis in lung,and negative regulation of pulmonary artery smooth muscle cell proliferation.Furthermore,Nur77also plays critical roles in inducing lung cancer and anti—cancer mechanism of retinoic acid.Therefore,the present paper reviews Nur77and its relationship with pulmonary diseases. 　　【Key words]Nur77;Ventilato卜induced lung injury;Cadmium—induced lung injury;Pulmonary artery hypertension;Lung cancer 　　Nur77(TR3,NR4A1)是一种孤儿核受体,属于 　　NR4A孤儿核受体超家族,广泛参与生物的炎症、代 　　谢、生长、分化及凋亡的调控。研究发现,许多肺部 　　疾病如呼吸机相关性肺损伤、镉中毒致肺损伤、肺动 　　脉高压及肺癌等常伴Nur77的高度表达,表明 　　Nur77在肺部疾病的发生、发展过程中起到一定作 　　用。对Nur77的深入研究可能是揭示肺部疾病发 　　病机制的一个新的方向。 　　1Nur77的结构与分布 　　Nur77又称神经生长因子诱导基因I—B,是 　　DOI:10.3760/cma.j.issn.1673—436X.2014.24.016 　　基金项目:国家自然科学基金;第二军医大学创新基 　　金(MS2013029);上海市浦江人才计划(14PJl411000) 　　作者单位:200