Inhibiting post-translational core fucosylation prevents vascular calcification in the model of uremia

Xu, Wen; Liu, Anqi; Yu, Chaoqin; Wang, Lingyu; Zhou, Ming; Wang, Nan; Fang, Ming; Wang, Weidong; Lin, Hongli

doi:10.1016/j.biocel.2016.08.015

Cited by 14 publications

(16 citation statements)

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“…In addition, transforming growth factor β (TGF‐β) signalling pathway is proven to promote VC, which is related to inflammation . High Pi induces activation of TGF‐β/Smad2/3 in VSMCs and Smads modulate specific genes transcription, including SMPD3/nSMase2 which converts sphingomyelin to ceramide . However, miR‐29b is proven to inhibit TGF‐β/Smad3 axis activation via targeting at Smad3 and alteration of exosomal miR‐29b modulates such mRNAs expression in the recipient infected cells concerning HIV study .…”

Section: Potential Regulatory Mechanisms Of Exosomes In Vcmentioning

confidence: 99%

Exosomes, the message transporters in vascular calcification

Zhang

Huang

et al. 2018

J Cellular Molecular Medi

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Vascular calcification (VC) is caused by hydroxyapatite deposition in the intimal and medial layers of the vascular wall, leading to severe cardiovascular events in patients with hypertension, chronic kidney disease and diabetes mellitus. VC occurrences involve complicated mechanism networks, such as matrix vesicles or exosomes production, osteogenic differentiation, reduced cell viability, aging and so on. However, with present therapeutic methods targeting at VC ineffectively, novel targets for VC treatment are demanded. Exosomes are proven to participate in VC and function as initializers for mineral deposition. Secreted exosomes loaded with microRNAs are also demonstrated to modulate VC procession in recipient vascular smooth muscle cells. In this review, we targeted at the roles of exosomes during VC, especially at their effects on transporting biological information among cells. Moreover, we will discuss the potential mechanisms of exosomes in VC.

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Section: Potential Regulatory Mechanisms Of Exosomes In Vcmentioning

confidence: 99%

Exosomes, the message transporters in vascular calcification

Zhang

Huang

et al. 2018

J Cellular Molecular Medi

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“…Lens culinaris agglutinin–fluorescein isothiocyanate (LCA-FITC; Vector Laboratories, Burlingame, USA) was used to detect the expression of core fucose; and staining was performed as described previously. [ 10 20 ]…”

Section: Ethodsmentioning

confidence: 99%

“…The siRNA sequences were validated using BLAST and the rat genome database to evaluate possible cross-reactivity, as described in our previous study. [ 10 20 ] Four siRNAs were synthesized and pooled, and dried siRNA pools were reconstituted in diethyl pyrocarbonate-treated water to a final concentration of 30 nmol/L and stored at −20°C until further use. For transfection, cells were incubated for 24 h to allow multiplication.…”

Section: Ethodsmentioning

confidence: 99%

“…Before HG stimulation, Fut8 siRNAs were transfected into rat PMCs using Lipofectamine ® 2000 from Invitrogen (Carlsbad, CA, USA) as previously described. [ 10 20 ] Real-time RT-PCR [ Figure 3a ] and Western blotting [ Figure 3b ] analysis confirmed that Fut8 siRNAs effectively decreased Fut8 mRNA (relative expression folds of HG + Fut8 group vs. HG group: 0.8 ± 0.1 vs. 1.5 ± 0.2, respectively, P = 0.031) and protein expression (relative expression folds of HG + Fut8 group vs. HG group: 3.6 ± 0.3 vs. 30.2 ± 1.3, respectively, P = 0.006). We then investigated the EMT status by HG stimulation after blockade of CF.…”

Section: R Esultsmentioning

confidence: 99%

“…More recently, emerging studies have suggested that posttranslational glycosylation modification of proteins plays a key role in altering protein functions, exerting profound effects on many important physiological and pathological processes, including cell growth, migration, and differentiation. [ 9 10 11 12 ] Core fucosylation (CF), which is catalyzed by α-1,6 fucosyltransferase (Fut8) in mammals,[ 13 ] is an important posttranslational glycosylation found to play a crucial role in pathological processes, including emphysema,[ 14 15 16 ] schizophrenia,[ 17 18 ] and hepatocellular carcinoma. [ 19 ] We recently demonstrated that diminishing the CF of transforming growth factor-β (TGF-β) receptors (TGF-βRs) blocked renal tubular EMT in cultured human renal proximal tubular epithelial cells in vitro and alleviated renal interstitial fibrosis in rats with unilateral ureteral obstruction.…”

Section: Introductionmentioning

confidence: 99%

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Blocking Posttranslational Core Fucosylation Ameliorates Rat Peritoneal Mesothelial Cell Epithelial-Mesenchymal Transition

Wang

et al. 2017

Chinese Medical Journal

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Background:Core fucosylation (CF), catalyzed by α-1,6 fucosyltransferase (Fut8) in mammals, plays an important role in pathological processes through posttranslational modification of key signaling receptor proteins, including transforming growth factor (TGF)-β receptors and platelet-derived growth factor (PDGF) receptors. However, its effect on peritoneal fibrosis is unknown. Here, we investigated its influence on epithelial-mesenchymal transition (EMT) of rat peritoneal mesothelial cells (PMCs) in vitro induced by a high-glucose (HG) culture solution.Methods:Rat PMCs were first cultured in a HG (2.5%) culture solution to observe the CF expression level (fluorescein isothiocyanate-lens culinaris agglutinin), we next established a knockdown model of rat PMCs in vitro with Fut8 small interfering RNA (siRNA) to observe whether inhibiting CF decreases the messenger RNA (mRNA) expression and protein expression of Fut8 and reverses EMT status. Rat PMCs were randomly divided into control group, mock group (transfected with scrambled siRNA), Fut8 siRNA group, HG group, HG + mock group, and HG + Fut8 siRNA group. Finally, we examined the activation of TGF-β/Smad2/3 signaling and PDGF/extracellular signal-regulated kinase (ERK) signaling to observe the influence of CF on them.Results:CF, Fut8 mRNA, and protein expression were all significantly upregulated in HG- induced EMT model than those in the control rat PMCs (P < 0.05). Fut8 siRNA successfully blocked CF of TGF-β receptors and PDGF receptors and attenuated the EMT status (E-cadherin and α-SMA and phenotypic changes) in HG-induced rat PMCs. In TGF-β/Smad2/3 signaling, Fut8 siRNA did not suppress the protein expression of TGF-β receptors and Smad2/3; however, it significantly suppressed the phosphorylation of Smad2/3 (relative expression folds of HG + Fut8 group vs. HG group: 7.6 ± 0.4 vs. 15.1 ± 0.6, respectively, P < 0.05). In PDGF/ERK signaling, Fut8 siRNA did not suppress the protein expression of PDGF receptors and ERK, but it significantly suppressed the phosphorylation of ERK (relative expression folds of HG + Fut8 group vs. HG group: 8.7 ± 0.9 vs. 15.6 ± 1.2, respectively, P < 0.05). Blocking CF inactivated the activities of TGF-β and PDGF signaling pathways, and subsequently blocked EMT.Conclusions:These results demonstrate that CF contributes to rat PMC EMT, and that blocking it attenuates EMT. CF regulation is a potential therapeutic target of peritoneal fibrosis.

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Up‐regulation of FUT8 inhibits TGF-β1-induced activation of hepatic stellate cells during liver fibrogenesis

Kuang

et al. 2021

Glycoconj J

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Inhibiting post-translational core fucosylation prevents vascular calcification in the model of uremia

Cited by 14 publications

References 50 publications

Exosomes, the message transporters in vascular calcification

Exosomes, the message transporters in vascular calcification

Blocking Posttranslational Core Fucosylation Ameliorates Rat Peritoneal Mesothelial Cell Epithelial-Mesenchymal Transition

Up‐regulation of FUT8 inhibits TGF-β1-induced activation of hepatic stellate cells during liver fibrogenesis

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