Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor

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	Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor
	Li, Huiping ; Yuan, Xiaobing ; Tang, Jun ; Zhang, Yongjun
刊名	AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
	2012
卷号	302 期号:6 页码:L569-L579
关键词	bronchopulmonary dysplasia cell polarity chorioamnionitis secondary septa transforming growth factor-alpha EPIDERMAL-GROWTH-FACTOR BRONCHOPULMONARY DYSPLASIA LUNG DEVELOPMENT FACTOR-ALPHA DIRECTED MIGRATION CELL-MIGRATION RAT MODEL FIBROBLASTS EXPRESSION MATURATION
ISSN号	1040-0605
通讯作者	Zhang, YJ (reprint author), Shanghai Jiao Tong Univ, MOE, Xin Hua Hosp, Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China,shanghaiyjzhang@yahoo.com.cn
英文摘要	Li H, Yuan X, Tang J, Zhang Y. Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor. Am J Physiol Lung Cell Mol Physiol 302: L569-L579, 2012. First published January 13, 2012; doi:10.1152/ajplung.00217.2011.-Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased alveolar number and increased airspace size. Formation of alveoli involves a process known as secondary septation triggered by myofibroblasts. This study investigated the underlying mechanisms of altered lung morphogenesis in a rat model of BPD induced by intra-amniotic injection of lipopolysaccharide (LPS). Results showed that LPS disrupted alveolar morphology and led to abnormal localization of myofibroblasts in the lung of newborn rats, mostly in primary septa with few in secondary septa. To identify potential mechanisms, in vitro experiments were carried out to observe the migration behavior of myofibroblasts. The migration speed of lung myofibroblasts increased with LPS treatment, whereas the directional persistence decreased. We found that LPS induced activation of EGFR and overexpression of its ligand, TGF-alpha in myofibroblasts. AG1478, an EGFR inhibitor, abrogated the enhanced locomotivity of myofibroblasts by LPS and also increased the directional persistence of myofibroblast migration. Myofibroblasts showed a high asymmetry of phospho-EGFR localization, which was absent after LPS treatment. Application of rhTGF-alpha to myofibroblasts decreased the directional persistence. Our findings indicated that asymmetry of phospho-EGFR localization in myofibroblasts was important for cell migration and its directional persistence. We speculate that LPS exposure disrupts the asymmetric localization of phospho-EGFR, leading to decreased stability of cell polarity and final abnormal location of myofibroblasts in vivo, which is critical to secondary septation and may contribute to the arrested alveolar development in BPD.
学科主题	Physiology ; Respiratory System
收录类别	SCI
资助信息	Shanghai Natural Science Foundation[11ZR1423800]; Shanghai Jiaotong University School of Medicine; Science Foundation for The Excellent Youth Scholars of Xinhua Hospital
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1496]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Li, Huiping,Yuan, Xiaobing,Tang, Jun,et al. Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor[J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,2012,302(6):L569-L579.
APA	Li, Huiping,Yuan, Xiaobing,Tang, Jun,&Zhang, Yongjun.(2012).Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor.AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,302(6),L569-L579.
MLA	Li, Huiping,et al."Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor".AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 302.6(2012):L569-L579.