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Title: Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor
Author: Li, Huiping ; Yuan, Xiaobing ; Tang, Jun ; Zhang, Yongjun
Source: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Issued Date: 2012
Volume: 302, Issue:6, Pages:L569-L579
Keyword: 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
Subject: Physiology ; Respiratory System
Corresponding Author: 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
English Abstract: 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.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1496
Appears in Collections:神经所(总)_期刊论文

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Li, Huiping; Yuan, Xiaobing; Tang, Jun; Zhang, Yongjun.Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor,AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,2012,302(6):L569-L579
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