Mechanisms of pulmonary fibrosis induced by core fucosylation in pericytes

Pulmonary fibrosis is a common outcome of a variety of pulmonary interstitial diseases, and myofibroblasts are the main culprit for this process. Recent studies have found that pericytes are one of the major sources of myofibroblasts; the transformation of which involves a complex process of activation of TGF-beta/Smad2/3 and PDGF beta/Erk signaling pathways. We have reported that the transforming growth factor -beta receptor and platelet derived growth factor -beta receptor (TGF-beta R I and PDGF beta R, respectively) are modified by glycosylation. Thus, we hope to regulate the above-mentioned signal pathways through core fucosylation (CF) catalyzed by alpha-1,6-fucosyltransferase (FUT8). Previous work has confirmed that TGF-beta 1 can induce the transformation of pericytes into myofibroblasts, while FUT8siRNA can inhibit such transformation. In the present study, we used an adenovirus packaging FUT8 shRNA to infect a bleomycin-induced pulmonary fibrosis mouse model and determined the effect of CF on pulmonary fibrosis by analyzing the mechanism of CF-mediated pericyte transformation. Our findings may shed new light on the mechanism of pulmonary interstitial fibrosis and provide a novel therapeutic target for clinical applications.