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

Abstract 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...

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Autores principales:	Manik C. Ghosh, Patrudu S. Makena, Joseph Kennedy, Bin Teng, Charlean Luellen, Scott E. Sinclair, Christopher M. Waters
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7d56ddc6eb64458599d6065d26ad94bf
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spelling	oai:doaj.org-article:7d56ddc6eb64458599d6065d26ad94bf2021-12-02T15:06:14ZA heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing10.1038/s41598-017-02204-22045-2322https://doaj.org/article/7d56ddc6eb64458599d6065d26ad94bf2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02204-2https://doaj.org/toc/2045-2322Abstract 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.Manik C. GhoshPatrudu S. MakenaJoseph KennedyBin TengCharlean LuellenScott E. SinclairChristopher M. WatersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manik C. Ghosh Patrudu S. Makena Joseph Kennedy Bin Teng Charlean Luellen Scott E. Sinclair Christopher M. Waters A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
description	Abstract 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.
format	article
author	Manik C. Ghosh Patrudu S. Makena Joseph Kennedy Bin Teng Charlean Luellen Scott E. Sinclair Christopher M. Waters
author_facet	Manik C. Ghosh Patrudu S. Makena Joseph Kennedy Bin Teng Charlean Luellen Scott E. Sinclair Christopher M. Waters
author_sort	Manik C. Ghosh
title	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_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_sort	heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7d56ddc6eb64458599d6065d26ad94bf
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A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing

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