PLX178259

GSE117489: Leading edge airway epithelial cell responses to in vitro wounding

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The airway epithelium of asthmatics is characterized by intrinsically abnormal wound repair that may contribute to disease pathobiology. In this study, we show that in asthma, the airway epithelial cells at the leading edge of a wound display aberrant migration patterns, reduced expression of 5 and 1 integrin subunits at baseline and during wound repair, resulting in dysregulated cell migration and an inability to fully repair. Transcriptional profiling identified the PI3K/Akt signaling pathway as the top upstream transcriptional regulator of integrin 51. Significantly, activation of Akt signaling enhanced airway epithelial repair in cultures derived from asthmatic children via upregulation of 5 and 1 integrin subunits. Conversely, inhibition of the PI3K/Akt signaling pathway in airway epithelial cultures from non-asthmatic children attenuated epithelial repair and reduced 5 and 1 integrin expression. Importantly, the FDA-approved drug celecoxib, and its non-COX2 inhibitory analogue dimethyl-celecoxib, also stimulated the PI3K/Akt/integrin 51 axis and restored airway epithelial repair in cells from asthmatics. Thus, targeting the PI3K/Akt pathway may represent a novel therapeutic avenue for asthma. SOURCE: Thomas Iosifidis (thomas.iosifidis@telethonkids.org.au) - Airway Epithelial Research Telethon Kids Institute