FIGURE 6.

Working model for onset of emphysema in Fut8^+/− mice upon exposure to CS. It was reported previously (15) that Fut8^−/− mice show emphysematous changes in the lung due to a lack of core fucosylation of the TGF-β1 receptor. In this study, Fut8 expression was down-regulated by exposure to CS, resulting a much lower level of core fucosylation. This change in N-glycosylation led to more severe impairment of the TGF-β1 signaling pathway. Moreover, CS evoked an up-regulation of Smad7, a key inhibitory factor associated with Smad2 phosphorylation. Comprehensively, a lower degree of core fucosylation appears to increase the susceptibility to CS-induced emphysemas. TβRI and TβRII, TGF-β receptors I and II, respectively; TF, transcription factor; ECM, extracellular matrix.