lncRNA-ES3/miR-34c-5p/BMF axis is involved in regulating high-glucose-induced calcification/senescence of VSMCs

Lin, Xiao; Zhan, Jicheng; Zhong, Jia‐Yu; Wang, Yanjiao; Wang, Yi; Li, Shuang; He, Jieyu; Tan, Pan; Chen, Yiyin; Liu, Xuebin; Cui, Xing‐Jun; Liu, You‐Shuo

doi:10.18632/aging.101758

Cited by 58 publications

(53 citation statements)

References 39 publications

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“…Renal replacement therapy including hemodialysis, peritoneal dialysis, and renal transplantation are the main treatments for patients with ESRD [2]. Vascular medial calci cation is mainly contributed to calcium and phosphate deposition [5,18]. In this study, there was no signi cant difference in blood lipid among patients with ESRD, RTR, and the healthy control.…”

Section: Discussionmentioning

confidence: 51%

“…Vascular calci cation is mainly characterized as the medial of aortic calci cation (termed as Mönckeberg's calci cation), and it often happens in patients with chronic kidney disease, especially end stage renal disease (ESRD) [1,2]. Lots of studies have demonstrated that vascular calci cation is not a simple passive process of calcium and phosphorus deposition but an active regulatory process, and the transdifferentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells is regarded to be the key pathophysiological factor of vascular calci cation [3][4][5]. However, the speci c mechanism of vascular calci cation in patients with ESRD is still not entirely elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Plasma exosomes derived from patients with end-stage renal disease and renal transplant recipients have different effects on vascular calcification

Lin

Zhu²,

Xing³

et al. 2020

Preprint

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Background End-stage renal disease (ESRD) patients usually develop extensive and progressive vascular calcification, and lots of calcification inhibitors as well as pro-calcifying factors are involved in the process. However, the mechanisms of vascular calcification in ESRD patients are still ill-defined. Methods The participants in the study were selected at the Second Xiangya Hospital, Central South University, and the plasma exosomes derived from ESRD patients (ESRD-Ex), renal transplant recipients (RTR-Ex), and the normal health control group (Nor-Ex) were isolated by ExoQuick-TC kit. Transmission electron microscopy and molecular size analysis were used to assess the morphology and size of exosomes. Alizarin Red S staining was carried out to detect calcification of vascular smooth muscle cells (VSMCs). Protein levels of Fetuin-A, matrix gla protein (MGP), Annexin-A2, bone morphogenetic protein (BMP-2), and receptor activator for nuclear factor-κ B ligand (Rankl) were measured by Western Blot analysis and the contents of that were detected using ELISA. Coronary artery calcification scores (CACS) were quantified via Agaston and analysed by Siemens CaScoring software. Results Compared with Nor-Ex, the ESRD-Ex promoted calcification of VSMCs significantly, and RTR-Ex could attenuate VSMCs calcification. Moreover, the protein concentration of ESRD-Ex was significantly higher than Nor-Ex and RTR-Ex, and the content of both MGP and Fetuin-A, the calcification inhibitors, were prominently lower in ESRD-Ex than those in Nor-Ex. The content of Annexin-A2, one of the calcification promoters, was significantly higher in ESRD-Ex and RTR-Ex than that in Nor-Ex. But, BMP-2 and Rankl had no significant difference among the three groups. In addition, the content of Fetuin-A in RTR-Ex was higher than that in ESRD-Ex, though it was still lower than in Nor-Ex. Furthermore, the content of both plasma Fetuin-A and MGP were negatively while that of Annexin-A2 was negatively correlated to CACS. Conclusions These results indicated that ESRD-Ex significantly promoted VSMCs calcification while renal transplantation could partially attenuate the effect of exosomes. Fetuin-A and MGP were decreased but Annexin-A2 was increased in ESRD-Ex, and renal transplantation could increase the level of Fetuin-A rather than MGP.

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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Plasma exosomes derived from patients with end-stage renal disease and renal transplant recipients have different effects on vascular calcification

Lin

Zhu²,

Xing³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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“…11 In previous work, we demonstrated that calcification/senescence of VSMCs is regulated by the lncRNA-ES3/miR-34c-5p/BMF axis. 12 However, that study did not elucidate the specific role of lncRNA-ES3 in calcification/senescence of VSMCs, and the overall mechanism remained largely uncharacterized.…”

Section: Introductionmentioning

confidence: 98%

LncRNA‐ES3 inhibition by Bhlhe40 is involved in high glucose–induced calcification/senescence of vascular smooth muscle cells

Zhong

Cui

Zhan

et al. 2020

Annals of the New York Academy of Sciences

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Long noncoding RNAs (lncRNAs) have been investigated as novel regulatory molecules involved in diverse biological processes. Our previous study demonstrated that lncRNA‐ES3 is associated with the high glucose–induced calcification/senescence of human aortic vascular smooth muscle cells (HA‐VSMCs). However, the mechanism of lncRNA‐ES3 in vascular calcification/aging remained largely unknown. Here, we report that the expression of basic helix‐loop‐helix family member e40 (Bhlhe40) was decreased significantly in HA‐VSMCs treated with high glucose, whereas the expression of basic leucine zipper transcription factor (BATF) was increased. Overexpression of Bhlhe40 and inhibition of BATF alleviated calcification/senescence of HA‐VSMCs, as confirmed by Alizarin Red S staining and the presence of senescence‐associated β‐galactosidase–positive cells. Moreover, we identified that Bhlhe40 regulates lncRNA‐ES3 in HA‐VSMCs by binding to the promoter region of the lncRNA‐ES3 gene (LINC00458). Upregulation or inhibition of lncRNA‐ES3 expression significantly promoted or reduced calcification/senescence of HA‐VSMCs, respectively. Additionally, we identified that lncRNA‐ES3 functions in this process by suppressing the expression of miR‐95‐5p, miR‐6776‐5p, miR‐3620‐5p, and miR‐4747‐5p. The results demonstrate that lncRNA‐ES3 triggers gene silencing of multiple miRNAs by binding to Bhlhe40, leading to calcification/senescence of VSMCs. Our findings suggest that pharmacological interventions targeting lncRNA‐ES3 may be therapeutically beneficial in ameliorating vascular calcification/aging.

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“…For example, lncRNA-ES3 can regulate calci cation/senescence of vascular smooth muscle cells through an miR-34c-5p/BMF axis that is activated upon HG induction. [38] The lncRNA SENCR shows high abundance of expression in vascular cells, [37,39,40] and can regulate fork-head box protein O1 and transient receptor potential cation channel 6, thereby promoting the proliferation and migration of smooth muscle cells. HG exposure of T2DM db/db mice can inhibit the expression and function in smooth muscle cells, and overexpression of SENCR reverses the inhibitory effect of HG on vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Analysis of long non-coding RNA expression profiles in high-glucose treated vascular endothelial cells

et al. 2020

Preprint

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Background: Diabetes mellitus is often associated with microvascular and macrovascular lesions, and hyperglycemia-induced vascular endothelial cell damage is a key factor. Methods： We investigated long non-coding RNAs (lncRNAs) and mRNAs that are affected by hyperglycemia-induced damage using human umbilical vein endothelial cells (HUVECs) as a model. HUVECs were cultured under high (25 mmol/L)or normal normal (5 mmol/L) glucose conditions for 6 d, and then lncRNAs and protein-coding transcripts were profiled by RNA-seq. Results： Among 40,379 lncRNAs screened, 214 were upregulated (log2 [fold-change] > 1, FDR < 0.05) and 197 were downregulated (log2 [fold-change] < −1, FDR < 0.05) in response to high-glucose. Furthermore, among 28,431 protein-coding genes screened, 778 were upregulated and 998 were downregulated. A total of 945 lncRNA/mRNA pairs were identified, including 126 differentially expressed lncRNAs predicted to target 201 mRNAs, among which 26 were cis-regulatory interactions. The corresponding lncRNA-mRNA network was composed of 354 lncRNA nodes, 1,167 mRNA nodes and 9,735 edges. Dozens of lncRNAs with high degree may play important roles in high-glucose-induced HUVEC damage, including ENST00000600527, NONHSAT037576.2, NONHSAT135706.2, ENST00000602127, NONHSAT200243.1, NONHSAT217282.1, NONHSAT176260.1, NONHSAT199075.1, NONHSAT067063.2, NONHSAT058417.2. Conclusion： These observations may provide novel insights into the regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction in diabetes-associated vascular disease.

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lncRNA-ES3/miR-34c-5p/BMF axis is involved in regulating high-glucose-induced calcification/senescence of VSMCs

Cited by 58 publications

References 39 publications

Plasma exosomes derived from patients with end-stage renal disease and renal transplant recipients have different effects on vascular calcification

Plasma exosomes derived from patients with end-stage renal disease and renal transplant recipients have different effects on vascular calcification

LncRNA‐ES3 inhibition by Bhlhe40 is involved in high glucose–induced calcification/senescence of vascular smooth muscle cells

Analysis of long non-coding RNA expression profiles in high-glucose treated vascular endothelial cells

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