RESULTS: Knockdown of AQP1 reduced basal proliferation and hypoxia-induced migration and proliferation in PASMCs. In subsequent experiments, wild-type AQP1, AQP1 lacking the entire cytoplasmic C-terminal tail or AQP1 with a mutation in the EF-hand motif were expressed in PASMCs using adenoviral constructs. Control cells expressed the same adenoviral construct containing green fluorescent protein. For all AQP1 constructs, infection increased AQP1 protein levels, water permeability and the change in cell volume induced by hypotonic challenge. Infection with wild-type and EF-hand mutated AQP1, but not C-terminal deleted AQP1, increased PASMC migration and proliferation.