Further, since CDDO activates PI3K-PKB/Akt signaling (reviewed in 53), the increase in Nrf2 activity in CF airway epithelial cells following treatment with CDDO (Nichols et al., 2009), suggests the reduced Nrf2 activity in preclinical models of CF lung disease is associated with GSK-3β activity. This evidence concerns the gene AKT1 and cystic fibrosis.