Mechanisms of pulmonary fibrosis induced by core fucosylation in pericytes |
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Institution: | 1. Departments of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, 222# Zhongshan Road, Dalian, Liaoning 116011, PR China;2. Departments of Nephrology, The First Affiliated Hospital of Dalian Medical University, 222# Zhongshan Road, Dalian, Liaoning 116011, PR China;3. From the Departments of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109;4. Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109 |
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Abstract: | 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-β/Smad2/3 and PDGFβ/Erk signaling pathways. We have reported that the transforming growth factor-β receptor and platelet-derived growth factor-β receptor (TGF-βR I and PDGFβR, respectively) are modified by glycosylation. Thus, we hope to regulate the above-mentioned signal pathways through core fucosylation (CF) catalyzed by α-1,6-fucosyltransferase (FUT8). Previous work has confirmed that TGF-β1 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. |
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Keywords: | Pulmonary fibrosis Pericyte Myofibroblasts Core fucosylation FUT8 |
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