However, in the honeycomb cysts of IPF and scleroderma lungs, canonical Notch signaling target HES1 is upregulated (Vaughan et al., 2015), indicating that the persistent activity of Notch signaling may result in malfunction of LNEPs and account for abnormal alveolar repair in interstitial lung diseases. This evidence concerns the gene HES1 and scleroderma.