miR-221 Alleviates the Ox-LDL-Induced Macrophage Inflammatory Response via the Inhibition of DNMT3b-Mediated NCoR Promoter Methylation

Ye, Jinshan; Wu, Yaxi; Guo, R. S.; Zeng, Wenjun; Duan, Yanan; Yang, Zhihua; Yang, Lixia

doi:10.1155/2019/4530534

Cited by 14 publications

(9 citation statements)

References 46 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 B). These results suggest that DNMT3B limits alternative macrophage polarization, corroborating previous reports [ 17 , 32 ]. Next to alternative macrophages, classically activated macrophages are present in the lungs of IPF patients [ 33 ].…”

Section: Resultssupporting

confidence: 92%

Myeloid DNA methyltransferase3b deficiency aggravates pulmonary fibrosis by enhancing profibrotic macrophage activation

et al. 2022

View full text Add to dashboard Cite

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and severe disease characterized by excessive matrix deposition in the lungs. Macrophages play crucial roles in maintaining lung homeostasis but are also central in the pathogenesis of lung diseases like pulmonary fibrosis. Especially, macrophage polarization/activation seems to play a crucial role in pathology and epigenetic reprograming is well-known to regulate macrophage polarization. DNA methylation alterations in IPF lungs have been well documented, but the role of DNA methylation in specific cell types, especially macrophages, is poorly defined. Methods In order to determine the role of DNA methylation in macrophages during pulmonary fibrosis, we subjected macrophage specific DNA methyltransferase (DNMT)3B, which mediates the de novo DNA methylation, deficient mice to the bleomycin-induced pulmonary fibrosis model. Macrophage polarization and fibrotic parameters were evaluated at 21 days after bleomycin administration. Dnmt3b knockout and wild type bone marrow-derived macrophages were stimulated with either interleukin (IL)4 or transforming growth factor beta 1 (TGFB1) in vitro, after which profibrotic gene expression and DNA methylation at the Arg1 promotor were determined. Results We show that DNMT3B deficiency promotes alternative macrophage polarization induced by IL4 and TGFB1 in vitro and also enhances profibrotic macrophage polarization in the alveolar space during pulmonary fibrosis in vivo. Moreover, myeloid specific deletion of DNMT3B promoted the development of experimental pulmonary fibrosis. Conclusions In summary, these data suggest that myeloid DNMT3B represses fibrotic macrophage polarization and protects against bleomycin induced pulmonary fibrosis.

show abstract

Section: Resultssupporting

confidence: 92%

Myeloid DNA methyltransferase3b deficiency aggravates pulmonary fibrosis by enhancing profibrotic macrophage activation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…23 As reported, DNMT3B inhibition remarkably inhibited ox-LDL-induced macrophage inflammatory. 36 In the current study, we found that DNMT3B expression was significantly elevated in AS patient tissues. Consistently, DNMT3B negatively regulated PTPN2 expression in ox-LDL-treated HUVECs.…”

Section: Discussionsupporting

confidence: 52%

DNMT3B activates FGFR3‐mediated endoplasmic reticulum stress by regulating PTPN2 promoter methylation to promote the development of atherosclerosis

et al. 2023

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress is closely associated with atherosclerosis (AS). Nevertheless, the regulatory mechanism of ER stress in endothelial cells during AS progression is unclear. Here, the role and regulatory mechanism of DNA (cytosine‐5‐)‐ methyltransferase 3 beta (DNMT3B) in ER stress during AS progression were investigated. ApoE−/− mice were fed with high fat diet to construct AS model in vivo. HE and Masson staining were performed to analyze histopathological changes and collagen deposition. HUVECs stimulated by ox‐LDL were used as AS cellular model. Cell apoptosis was examined using flow cytometry. DCFH‐DA staining was performed to examine ROS level. The levels of pro‐inflammatory cytokines were assessed using ELISA. In addition, MSP was employed to detect PTPN2 promoter methylation level. Our results revealed that DNMT3B and FGFR3 were significantly upregulated in AS patient tissues, whereas PTPN2 was downregulated. PTPN2 overexpression attenuate ox‐LDL‐induced ER stress, inflammation and apoptosis in HUVECs and ameliorated AS symptoms in vivo. PTPN2 could suppress FGFR3 expression in ox‐LDL‐treated HUVECs, and FGFR3 knockdown inhibited ER stress to attenuate ox‐LDL‐induced endothelial cell apoptosis. DNMT3B could negatively regulate PTPN2 expression and positively FGFR2 expression in ox‐LDL‐treated HUVECs; DNMT3B activated FGFR2 expression by increasing PTPN2 promoter methylation level. DNMT3B downregulation repressed ox‐LDL‐induced ER stress, inflammation and cell apoptosis in endothelial cells, which was reversed by PTPN2 silencing. DNMT3B activated FGFR3‐mediated ER stress by increasing PTPN2 promoter methylation level and suppressed its expression, thereby boosting ER stress to facilitate AS progression.

show abstract

“…On the one hand, ox-LDL activates numerous inflammatory factors and promotes inflammatory cell infiltration. On the other hand, activated macrophage cytophagy and degraded ox-LDL lead to the accumulation of cholesterol and formation of foam cells [26,27]. These data suggest that TNF-α and IL-6 were enhanced during foam cell formation, but this effect was reversed synergistically by MP and LOX-1 gene silencing, indicating that LOX-1 inhibition and MP intervention could synergistically and markedly suppress foam cell formation.…”

Section: Discussionmentioning

confidence: 99%

Synergistic anti-atherosclerotic effect of Yerba Maté (Illex Paraguariensis) polyphenols and Lox-1 silencing in foam cell model

Yu¹,

Fu²,

Yin³

et al. 2021

Trop. J. Pharm Res

View full text Add to dashboard Cite

Purpose: To elucidate the anti-atherosclerotic effect of Yerba Mate polyphenols (MP) as well as the anti-atherosclerotic effect of a combination of MP and silencing of lectin-like oxidized low-density lipoprotein receptor-1 interference group (LOX)-1.Methods: The anti-atherosclerotic effects of control group (CG), simvastatin group (SG), MP group (MP), LOX-1 interference group (LOX) and MP + LOX-1 interference group (MP-LOX) were determined using Oil Red O staining, enzyme-linked immunosorbent assay (ELISA) and Western blot assay.Results: The levels of foam cells, intracellular lipids, viz, total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE) and acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1); LOX-1, inflammation (TNF-alpha, IL-6 and pNF-κB/NF-κB); adhesion molecular status (ICAM-1 and VCAM-1), and monocyte chemotactic protein-1 in SG and in MP, LOX and MP-LOX groups were significantly decreased, when compared with CG (p < 0.01). The levels of these parameters were much lower in MPLOX group than in SG (p < 0.01). However, they were synergistically reduced in MP-LOX group, relative to MP group or LOX group (p < 0.01). Combination of LOX-1 gene silencing with MP produced synergistic anti-atherosclerotic effect which was reflected in decreases in foam cell formation, intracellular lipids, inflammatory status, adhesion molecular status, and MCP-1-mediated migration and infiltration of macrophages in foam cells.Conclusion: The synergistic anti-atherosclerotic effects of MP and LOX-1 gene silencing may be potential tools for development of anti-atherosclerotic agents.

show abstract

miR-221 Alleviates the Ox-LDL-Induced Macrophage Inflammatory Response via the Inhibition of DNMT3b-Mediated NCoR Promoter Methylation

Cited by 14 publications

References 46 publications

Myeloid DNA methyltransferase3b deficiency aggravates pulmonary fibrosis by enhancing profibrotic macrophage activation

Myeloid DNA methyltransferase3b deficiency aggravates pulmonary fibrosis by enhancing profibrotic macrophage activation

DNMT3B activates FGFR3‐mediated endoplasmic reticulum stress by regulating PTPN2 promoter methylation to promote the development of atherosclerosis

Synergistic anti-atherosclerotic effect of Yerba Maté (Illex Paraguariensis) polyphenols and Lox-1 silencing in foam cell model

Contact Info

Product

Resources

About