Rho Signaling Regulates Pannexin 1-mediated ATP Release from Airway Epithelia

摘要: ATP released from airway epithelial cells promotes purinergic receptor-regulated mucociliary clearance activities necessary for innate lung defense. Cell swelling-induced membrane stretch/strain is a common stimulus that release, but the mechanisms transducing cell swelling into release are incompletely understood. Using knockdown and knockout approaches, we tested hypothesis pannexin 1 mediates hypotonically swollen epithelia investigated regulating this activity. Well differentiated primary cultures of human bronchial subjected to hypotonic challenge exhibited enhanced which was paralleled by uptake probe propidium iodide. Both responses were reduced inhibitors knocking down 1. Importantly, hypotonicity-evoked freshly excised tracheas dye in tracheal impaired mice. Hypotonicity-promoted well accompanied RhoA activation myosin light chain phosphorylation dominant negative mutant RhoA(T19N) Rho kinase inhibitors. highly selective transient receptor potential vanilloid 4 (TRPV4). Lastly, TRPV4 release. Our data suggest transduce 1-mediated epithelia.