TGFB1 and chronic obstructive pulmonary disease: Interestingly, Notch3 down-regulation was observed in smokers and in COPD lung, making it a potential target for controlling the balance between basal and luminal cells [16, 56] Candidate pathways for targeting in COPD include Hedgehog signaling, Notch signaling, the retinoic acid pathway and the transforming growth factor-β (TGF-β) pathway [57].