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

Manik C. Ghosh, Patrudu S. Makena, Joseph Kennedy, Bin Teng, Charlean Luellen, Scott E. Sinclair, Christopher M. Waters

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Article number2155
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Bibliographical note

Funding Information:
These studies were supported by National Heart, Lung, and Blood Institute grant HL-123540 (CMW).

Publisher Copyright:
© 2017 The Author(s).

ASJC Scopus subject areas

  • General

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