Inhibiting post-translational core fucosylation prevents vascular calcification in the model of uremia
Autor: | Mengying Zhou, Wen Xinyu, Ming Fang, Hongli Lin, Nan Wang, Changqing Yu, Anqi Liu, Lingyu Wang, Weidong Wang |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Male Fucosyltransferase Vascular smooth muscle Receptor Transforming Growth Factor-beta Type I Smad Proteins SMAD Protein Serine-Threonine Kinases Biochemistry Phosphates Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Transforming Growth Factor beta medicine Animals Humans Phosphorylation RNA Small Interfering Receptor Vascular Calcification Fucosylation Fucose Uremia biology Chemistry Cell Biology Transforming growth factor beta medicine.disease Fucosyltransferases Cell biology Rats Up-Regulation Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Gene Knockdown Techniques Radial Artery biology.protein Signal transduction Protein Processing Post-Translational Receptors Transforming Growth Factor beta Calcification Signal Transduction |
Zdroj: | The international journal of biochemistrycell biology. 79 |
ISSN: | 1878-5875 |
Popis: | Vascular calcification (VC) is an independent risk factor for cardiovascular disease and mortality in uremia. Post-translational core fucosylation is implicated in a number of pathological processes. First, we investigated the role of core fucosylation and key TGF-β1 pathway receptors in calcified arteries in vivo. To determine whether blocking core fucosylation effectively inhibited VC and TGF-β/Smad signaling pathway, we established an in vitro model of phosphate-induced calcification in rat vascular smooth muscle cells (VSMCs) to assess the role of core fucosylation in VC. Core fucose could be detected at markedly higher levels in calcified VSMCs than control cells. Fut8 (α-1,6 fucosyltransferase), the only enzyme responsible for core fucosylation in humans, was significantly upregulated by high phosphate. Exposed to high phosphate media and blocking core fucosylation in VSMCs by knocking down Fut8 using a siRNA markedly reduced calcium and phosphorus deposition and Cbfα1 expression (osteoblast-specific transcription factor), and increased α-Sma expression (smooth muscle cell marker). Fut8 siRNA significantly inhibited TGF-β/Smad2/3 signaling activation in VSMCs cultured in high phosphate media. In conclusion, this study provides evidence to suggest core fucosylation plays a major role in the process of VC and appropriate blockade of core fucosylation may represent a potential therapeutic strategy for treating VC in end-stage renal disease. |
Databáze: | OpenAIRE |
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