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
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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