Csk/Src/EGFR signaling regulates migration of myofibroblasts and alveolarization

American Journal of Physiology. Lung Cellular and Molecular Physiology
Jianhui LiYongjun Zhang

Abstract

Bronchopulmonary dysplasia (BPD) is characterized by premature alveolar developmental arrest. Antenatal exposure to inflammation inhibits lung morphogenesis, thus increasing the risk of developing BPD. Alveolar myofibroblasts are thought to migrate into the septal tips and elongate secondary septa during alveolarization. Here we found lipopolysaccharide (LPS) disrupted the directional migration of myofibroblasts and increased actin stress fiber expression and focal adhesion formation. In addition, COOH-terminal Src kinase (Csk) activity was downregulated in myofibroblasts treated with LPS, while activation of Src or epidermal growth factor receptor (EGFR) was upregulated by LPS treatment. Specifically, decreased Csk activity and increased activation of Src or EGFR was also observed in primary myofibroblasts isolated from newborn rat lungs with intra-amniotic LPS exposure, a model for BPD. Further investigation revealed that EGFR was involved in cell migration impairment induced by LPS, and Src inhibition blocked LPS-induced activation of EGFR or cell migration impairment. Csk silencing also resulted in EGFR activation and cell migration impairment. Besides, we found the effect of EGFR on myofibroblast migration was mediated thr...Continue Reading

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Citations

Jul 1, 2016·Molecular and Cellular Pediatrics·Tayyab ShahzadHarald Ehrhardt
Dec 13, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer M S SucreBrigitte N Gomperts
Oct 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E Surate SolaligueRory E Morty
Mar 13, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer M S SucreBrigitte N Gomperts
Aug 24, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Chao HuLin Cai

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