Cigarette smoke impairs airway epithelial wound repair: role of modulation of epithelial-mesenchymal transition processes and notch-1 signaling

Vincenzo, S. di; Ninaber, D.K.; Cipollina, C.; Ferraro, M.; Hiemstra, P.S.; Pace, E. (2022)

Article / Letter to editor

Cigarette smoke (CS) induces oxidative stress and chronic inflammation in airway epithelium. It is a major risk factor for respiratory diseases, characterized by epithelial injury. The impact of CS on airway epithelial repair, which involves epithelial-mesenchymal transition (EMT) and the Notch-1 pathway, is incompletely understood. In this study, we used primary bronchial epithelial cells (PBECs) to evaluate the effect of CS on epithelial repair and these mechanisms. The effect of CS and/or TGF-beta1 on wound repair, various EMT and Notch-1 pathway markers and epithelial cell markers (TP63, SCGB1A) was assessed in PBECs cultured submerged, at the air-liquid interface (ALI) alone and in co-culture with fibroblasts. TGF-beta1 increased epithelial wound repair, activated EMT (shown by decrease in E-cadherin, and increases in vimentin, SNAIL1/SNAIL2/ZEB1), and increased Notch-1 pathway markers (NOTCH1/JAGGED1/HES1), MMP9, TP63, SCGB1A1. In contrast, CS decreased wound repair and vimentin, NOTCH1/JAGGED1/HES1, MMP9, TP63, SCGB1A1, whereas it activated the initial steps of the EMT (decrease in E-cadherin and increases in SNAIL1/SNAIL2/ZEB1). Using combined exposures, we observed that CS counteracted the effects of TGF-beta1. Furthermore, Notch signaling inhibition decreased wound repair. These data suggest that CS inhibits the physiological epithelial wound repair by interfering with the normal EMT process and the Notch-1 pathway.

• cigarette smoke
• proximal airways
• repair processes
• epithelial-mesenchymal transition
• TGF-beta1
• Notch-1 pathway

• All authors: Vincenzo, S. di; Ninaber, D.K.; Cipollina, C.; Ferraro, M.; Hiemstra, P.S.; Pace, E.
• Date: 2022-10-01
• Journal: Antioxidants
• Volume: 11
• Issue: 10
• DOI: doi:10.3390/antiox11102018