Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury

	Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury
	Zhang, Y; Jiang, G; Sauler, M; Lee, PJ
刊名	FASEB JOURNAL
	2013
卷号	27 期号:10 页码:4041-4058
关键词	cell death VE-cadherin heat-shock protein
通讯作者	Lee, PJ (reprint author), Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, POB 208057, New Haven, CT 06520 USA.,patty.lee@yale.edu
英文摘要	The lung endothelium is a major target for inflammatory and oxidative stress. Heme oxygenase-1 (HO-1) induction is a crucial defense mechanism during oxidant challenges, such as hyperoxia. The role of lung endothelial HO-1during hyperoxia in vivo is not well defined. We engineered lentiviral vectors with microRNA (miRNA) sequences controlled by vascular endothelium cadherin (VE-cad) to study the specific role of lung endothelial HO-1. Wild-type (WT) murine lung endothelial cells (MLECs) or WT mice were treated with lentivirus and exposed to hyperoxia (95% oxygen). We detected HO-1 knockdown (approximate to 55%) specifically in the lung endothelium. MLECs and lungs showed approximately a 2-fold increase in apoptosis and ROS generation after HO-1 silencing. We also demonstrate for the first time that silencing endothelial HO-1 has the same effect on lung injury and survival as silencing HO-1 in multiple lung cell types and that HO-1 regulates caspase 3 activation and autophagy in endothelium during hyperoxia. These studies demonstrate the utility of endothelial-targeted gene silencing in vivo using lentiviral miRNA constructs to assess gene function and that endothelial HO-1 is an important determinant of survival during hyperoxia.Zhang, Y., Jiang, G., Sauler, M., Lee, P. J. Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury.
学科主题	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Biology ; Cell Biology
关键词[WOS]	SMALL INTERFERING RNA ; HEME OXYGENASE-1 ; CONFERS SUSCEPTIBILITY ; GENE-TRANSCRIPTION ; MAMMALIAN-CELLS ; PROTECTIVE ROLE ; EXPRESSION ; MICE ; VECTORS ; FISSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000329747100018
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/433]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhang, Y,Jiang, G,Sauler, M,et al. Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury[J]. FASEB JOURNAL,2013,27(10):4041-4058.
APA	Zhang, Y,Jiang, G,Sauler, M,&Lee, PJ.(2013).Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury.FASEB JOURNAL,27(10),4041-4058.
MLA	Zhang, Y,et al."Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury".FASEB JOURNAL 27.10(2013):4041-4058.