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

Scientific Reports
Manik C GhoshChristopher M Waters

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 phosp...Continue Reading

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Citations

Mar 5, 2019·Cellular and Molecular Life Sciences : CMLS·Laura PatrussiCosima T Baldari
Jan 17, 2020·Scientific Reports·Mingxing FangZhiyong Wang

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Methods Mentioned

BETA
immunoprecipitation
electrophoresis
scraping
X-ray

Software Mentioned

Image
Sigmastat
Metamorph

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