Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract-induced emphysema in animal model

He, Zhijun; Chen, Yan; Chen, Ping; He, Shengdong; Ye, Jiru; Li, Da

doi:10.1177/1535370215598402

Cited by 14 publications

(19 citation statements)

References 40 publications

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“…Lung function was measured using a small animal spirometer (PLY3211 system; Buxco Electronics, Sharon, CT, USA) as previously described with a minor modification . Briefly, each mouse was weighed, anesthetized by intraperitoneal injection of 10% chloral hydrate (3 ml/kg BW) and tracheostomized.…”

Section: Methodsmentioning

confidence: 99%

PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice

Xie

et al. 2017

Scand J Immunol

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Macrophages play an important role in the pathogenesis of COPD. Macrophage polarization towards the M2 phenotype has been observed in the lung tissues of COPD patients and cigarette smokers. The molecular basis of this process remains unclear, and it has not been completely illuminated in animal models of emphysema. In our study, we combined cigarette smoke (CS) exposure with intraperitoneal injection of cigarette smoke extract (CSE) to build an emphysema model. We found by immunohistochemical staining and flow cytometry that the expression level of CD206 and the ratio of M2 to M1 macrophages was increased in emphysematous mice. We also demonstrated that decreased protein level for phosphatase and tensin homology deleted on chromosome ten (PTEN) and increased total protein levels for phosphorylation -protein kinase B (p-AKT) in the lung tissue of emphysematous mice and in CSE-treated RAW264.7 cells. In both bone marrow-derived macrophages (BMDMs) from emphysematous mice and CSE-treated RAW264.7 cells, we observed by RT-PCR that the mRNA levels of M2 macrophage-related markers and cytokines were increased. Furthermore, M1 macrophage-related markers and cytokines were decreased. Meanwhile we treated BMDMs from emphysematous mice and CSE-treated RAW264.7 cells with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor (LY294002), we observed a reduction in RNA levels of M2 macrophage-related markers and cytokines. In conclusion, we confirmed that macrophage M2 polarization was induced in emphysematous mice generated by CS exposure combined with intraperitoneal injection of CSE. We also showed that M2 polarization was mediated through PTEN/PI3k/AKT pathway activation.

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Section: Methodsmentioning

confidence: 99%

PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice

Xie

et al. 2017

Scand J Immunol

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“…Mononuclear cells (MNCs) from the bone marrow of C57BL/6J mice were isolated via Ficoll density gradient centrifugation (Histopaque-1083, Sigma, Santa Clara, CA, USA) before being inoculated into culture flasks at a density of (3~5)×10 6 /ml and cultured with EGM-2 in 5% FBS (SingleQuots ® , Lonza, Basel, Switzerland) under an atmosphere of 95% humidity and 5% CO 2 at 37°C [ 15 ]. On day 4 of the culture, the culture fluid was replaced with fresh culture medium to remove the unattached cells.…”

Section: Methodsmentioning

confidence: 99%

“…Cell harvesting was performed on day 7 of the culture. Double-positive staining of Ulex europaeus agglutinin-1(UEA-1) lectin and acetylated low-density lipoprotein (acLDL) was used for EPCs identification [ 15 ]. Briefly, the harvested cells were incubated with 7.5 μg/ml 1,1′-dioctadecyl-3,3,3′,3-tetramethylindocarbocyanine perchlorate(Dil)-labeled acLDL (Dil-acLDL, Molecular Probes, Eugene, OR, USA) at 37°C for 4 h and fixed with 4% paraformaldehyde for 10 min.…”

Section: Methodsmentioning

confidence: 99%

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Cigarette Smoke Extract Changes Expression of Endothelial Nitric Oxide Synthase (eNOS) and p16(INK4a) and is Related to Endothelial Progenitor Cell Dysfunction

Chen

Hou

et al. 2017

Med Sci Monit

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BackgroundEndothelial dysfunction is an important pathophysiologic feature in many smoke-related diseases. Endothelial progenitor cells (EPCs) are the precursors of endothelial cells and play a fundamental role in the maintenance of endothelial integrity and function. Endothelial nitric oxide synthase (eNOS) is the dominant NOS isoform in the vasculature and plays a central role in the maintenance of endothelial homeostasis. p16(INK4a) is a cyclin-dependent kinase inhibitor and could be regarded as a major dominant senescence gene. The present study aimed to determine whether the expression of eNOS and p16(INK4a) in EPCs is related to EPCs function and the possible epigenetic mechanism, if any.Material/MethodsWe investigated EPCs capacity for proliferation, adhesion, and secretion, and the expression of eNOS and p16(INK4a) in EPCs which were altered by cigarette smoke extract (CSE) in vitro. Furthermore, Decitabine (Dec), an agent of demethylation, was used to examine whether it could alter the changes induced by CSE.ResultsThe present study demonstrated that EPCs altered by CSE in vitro displayed decreased capacities of proliferation, adhesion, and secretion, which was accompanied by decreased eNOS expression and increased p16(INK4a) expression in EPCs. Furthermore, Dec could alleviate the changes in the expression of eNOS and p16(INK4a), and protect against the EPCs dysfunction caused by CSE.ConclusionsThe decreased eNOS expression and increased p16(INK4a) expression was associated with dysfunction of EPCs caused by CSE. The mechanism of methylation, one of the most common epigenetic mechanism, may be involved in the EPCs dysfunction caused by CSE.

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“…From the bioinformatics directly we can ascertain if there are CG dinucleotides in the Sca-1 promoter sequence ( http://www.urogene.org/ methprimer/). In terms of previous experiments, it was suggested that the regulation of methylation may participate in Sca-1 expression 23 . Decitabine (Dec) is a demethylation reagent and widely used in medical treatment, it can activate demethylation in vitro and in vivo 24 and make epigenetic silencing genes reactivate again 25 .…”

Section: Introductionmentioning

confidence: 87%

Cigarette smoke extract affects methylation status and attenuates Sca-1 expression of mouse endothelial progenitor cell <i>in vitro</i>

He¹,

Chen²,

Chen³

et al. 2021

Tob. Induc. Dis.

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INTRODUCTION Endothelial dysfunction appears in many smoking-related diseases, it is also an important pathophysiological feature. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and have a crucial effect on the repair and maintenance of endothelial integrity. Sca-1 is not only common in bone marrow-derived hematopoietic stem cells (HSCs), but it is also expressed in nonhematopoietic organs by tissue-resident stem and progenitor cells. The aim of this study is to investigate the impact of cigarette smoke extract (CSE) on the function of bone marrow-derived EPCs and the expression level of Sca-1 in EPCs, and also whether the methylation of Sca-1 is involved in EPC dysfunction. METHODS We measured EPC capacities including adhesion, secretion and proliferation, the concentration of endothelial nitric oxide synthase (eNOS) and apoptosis-inducing factor (AIF) in cell culture supernatant, and also Sca-1 expression and promoter methylation in EPCs induced by CSE. Decitabine (Dec) was applied to test whether it could alter the impact caused by CSE. RESULTS The adhesion, proliferation and secretion ability of EPCs can be induced to be decreased by CSE in vitro , accompanied by decreased concentrations of AIF and eNOS in cell culture supernatant and decreased Sca-1 expression in EPCs. In addition, Dec could partly attenuate the impact described above. There were no significant differences in the quantitative analysis of Sca-1 promoter methylation among different groups. CONCLUSIONS The decreased Sca-1 expression was related to EPC dysfunction induced by CSE. EPC dysfunction resulting from CSE may be related to methylation mechanism, but not the methylation of Sca-1 promoter.

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Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract-induced emphysema in animal model

Cited by 14 publications

References 40 publications

PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice

PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice

Cigarette Smoke Extract Changes Expression of Endothelial Nitric Oxide Synthase (eNOS) and p16(INK4a) and is Related to Endothelial Progenitor Cell Dysfunction

Cigarette smoke extract affects methylation status and attenuates Sca-1 expression of mouse endothelial progenitor cell <i>in vitro</i>

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