Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor
Open Access
- 15 March 2012
- journal article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 302 (6), L569-L579
- https://doi.org/10.1152/ajplung.00217.2011
Abstract
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-α 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-α 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.Keywords
This publication has 49 references indexed in Scilit:
- Cell behaviors regulated by guidance cues in collective migration of border cellsThe Journal of cell biology, 2011
- Hypoxic remodelling of Ca2+ stores does not alter human cardiac myofibroblast invasionBiochemical and Biophysical Research Communications, 2010
- Myosin VI and Optineurin Are Required for Polarized EGFR Delivery and Directed MigrationTraffic, 2010
- Lung interstitial cells during alveolarizationKorean Journal of Pediatrics, 2010
- The role of integrin α8β1 in fetal lung morphogenesis and injuryDevelopmental Biology, 2009
- FGF signaling is required for myofibroblast differentiation during alveolar regenerationAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Role of Ureaplasma Species in Neonatal Chronic Lung Disease: Epidemiologic and Experimental EvidencePediatric Research, 2009
- A Primary Role for Golgi Positioning in Directed Secretion, Cell Polarity, and Wound HealingMolecular Biology of the Cell, 2009
- Loss of protein kinase Cϵ results in impaired cutaneous wound closure and myofibroblast functionJournal of Cell Science, 2008
- Bronchopulmonary dysplasia of the premature babyPediatric Pulmonology, 1997