Fig. 8.

Proposed model for the role of vimentin phosphorylation and YAP1 in Cd-induced peribronchiolar fibrosis, airway remodeling, and subsequent COPD. Prolonged exposure to Cd results in fibrosis around the airways. Cd-induced phosphorylation of AKT and cdc2 kinase is required for the vimentin phosphorylation at Ser³⁹ and Ser⁵⁵, respectively. Such phosphorylated vimentin will bind 14-3-3 and facilitate the nuclear translocation of YAP1 and Smad2/3 and complex formation of YAP1 and Smad2/3 in the nucleus, which activates myofibroblast and induces ECM protein deposition.