| The Rac1/JNK pathway is critical for EGFR-dependent barrier formation in human airway epithelial cells. | |
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MedLine Citation:
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PMID: 21036915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The airway epithelial barrier provides defenses against inhaled antigens and pathogens, and alterations of epithelial barrier function have been proposed to play a significant role in the pathogenesis of chronic airway diseases. Although the epidermal growth factor receptor (EGFR) plays roles in various physiological and pathological processes on the airway epithelium, the role of EGFR on barrier function in the airway remains largely unknown. In the present study, we assessed the effects of EGFR activation on paracellular permeability in airway epithelial cells (AECs). EGFR activation induced by the addition of EGF increased transepithelial electrical resistance (TER) in AECs. An EGFR-blocking antibody eradicated the development of TER, paracellular influx of dextran, and spatial organization of tight junction. Moreover, the effects of EGFR activation on paracellular permeability were eradicated by knockdown of occludin. To identify the EGFR signaling pathway that regulates permeability barrier development, we investigated the effects of several MAP kinase inhibitors on permeability barrier function. Pretreatment with a JNK-specific inhibitor, but not an ERK- or p38-specific inhibitor, attenuated the development of TER induced by EGFR activation. Rac1 is one of the upstream activators for JNK in EGFR signaling. Rac1 knockdown attenuated the phosphorylation of JNK activation and EGFR-mediated TER development. These results suggest that EGFR positively regulates permeability barrier development through the Rac1/JNK-dependent pathway. |
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Authors:
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Masahiro Terakado; Yasuhiro Gon; Akiko Sekiyama; Ikuko Takeshita; Yutaka Kozu; Ken Matsumoto; Noriaki Takahashi; Shu Hashimoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-29 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 300 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-20 Completed Date: 2011-01-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L56-63 Citation Subset: IM |
Affiliation:
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Dept. of Internal Medicine, Nihon Univ. School of Medicine, Tokyo, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Airway Obstruction
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physiopathology* Cell Membrane Permeability / drug effects, physiology Epidermal Growth Factor / pharmacology Epithelial Cells / drug effects, physiology* Humans Lung / physiology* MAP Kinase Kinase 4 / metabolism* MAP Kinase Signaling System / physiology* Mitogen-Activated Protein Kinases / metabolism Receptor, Epidermal Growth Factor / drug effects, immunology, physiology* Tight Junctions / drug effects, physiology rac1 GTP-Binding Protein / physiology* |
| Chemical | |
Reg. No./Substance:
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62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 4; EC 3.6.5.2/rac1 GTP-Binding Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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