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A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing

Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epitheli...

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Autores principales: Ghosh, Manik C., Makena, Patrudu S., Kennedy, Joseph, Teng, Bin, Luellen, Charlean, Sinclair, Scott E., Waters, Christopher M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438388/
https://www.ncbi.nlm.nih.gov/pubmed/28526890
http://dx.doi.org/10.1038/s41598-017-02204-2
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author Ghosh, Manik C.
Makena, Patrudu S.
Kennedy, Joseph
Teng, Bin
Luellen, Charlean
Sinclair, Scott E.
Waters, Christopher M.
author_facet Ghosh, Manik C.
Makena, Patrudu S.
Kennedy, Joseph
Teng, Bin
Luellen, Charlean
Sinclair, Scott E.
Waters, Christopher M.
author_sort Ghosh, Manik C.
collection PubMed
description Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4. In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric complex, while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex. Cell migration following wounding was decreased when PP5 expression was decreased using shRNA, but migration was increased in ATII cells isolated from ASK1 knockout mice. Interactions between FAK and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP5 was depleted. Furthermore, we found that wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine phosphorylation of FAK, and decreased association of phosphorylated ASK1 with FAK. These changes in phosphorylation were dependent upon expression of PP5. These results demonstrate a unique molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.
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spelling pubmed-54383882017-05-22 A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing Ghosh, Manik C. Makena, Patrudu S. Kennedy, Joseph Teng, Bin Luellen, Charlean Sinclair, Scott E. Waters, Christopher M. Sci Rep Article Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4. In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric complex, while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex. Cell migration following wounding was decreased when PP5 expression was decreased using shRNA, but migration was increased in ATII cells isolated from ASK1 knockout mice. Interactions between FAK and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP5 was depleted. Furthermore, we found that wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine phosphorylation of FAK, and decreased association of phosphorylated ASK1 with FAK. These changes in phosphorylation were dependent upon expression of PP5. These results demonstrate a unique molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing. Nature Publishing Group UK 2017-05-19 /pmc/articles/PMC5438388/ /pubmed/28526890 http://dx.doi.org/10.1038/s41598-017-02204-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ghosh, Manik C.
Makena, Patrudu S.
Kennedy, Joseph
Teng, Bin
Luellen, Charlean
Sinclair, Scott E.
Waters, Christopher M.
A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
title A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
title_full A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
title_fullStr A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
title_full_unstemmed A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
title_short A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
title_sort heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438388/
https://www.ncbi.nlm.nih.gov/pubmed/28526890
http://dx.doi.org/10.1038/s41598-017-02204-2
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