BioProject

The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. More...

The mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a disruption of the epidermal barrier, water is lost resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as the sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators. The same pathways are present in lung epithelial cells. A signal transduction pathway mediated directly through Nax and secondarily through ENaC results in production of secretory inflammatory mediators. These mediators result in epithelial proliferation and restoration of epidermal homeostasis, but can also have negative effects including excess inflammation and ultimately leads to activation of fibroblasts. Overall design: Both wild type and Nax knockdown HaCaT cells were seeded in 12-well plates. 70-80% confluent cells were starved with fetal bovine serum (FBS) free Dulbecco's modified Eagle's medium (DMEM) overnight followed by a treatment with control medium (final150 mM sodium) or medium plus 10% more sodium (final 165 mM sodium). Cells were harvested at time point 0, 4, and 16 hours post treatment. Less...