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Hyperoxia-induced methylation decreases RUNX3 in a newborn rat model of bronchopulmonary dysplasia

Overview of attention for article published in Respiratory Research, June 2015
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  • Above-average Attention Score compared to outputs of the same age (52nd percentile)
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Title
Hyperoxia-induced methylation decreases RUNX3 in a newborn rat model of bronchopulmonary dysplasia
Published in
Respiratory Research, June 2015
DOI 10.1186/s12931-015-0239-x
Pubmed ID
Authors

Yuting Zhu, Jianhua Fu, Haiping Yang, Yuqing Pan, Li Yao, Xindong Xue

Abstract

Bronchopulmonary dysplasia (BPD) in premature infants is a predominantly secondary occurrence to intrauterine inflammation/infection and postpartum mechanical ventilation; in recent years, an association with epigenetics has also been found. DNA methylation, catalyzed by DNA methyl transferases (DNMTs), and tri-methylation of lysine 27 on histone H3 (H3K27me3), mediated by the methyltransferase, Enhancer of Zeste Homolog 2 (EZH2), are some of the most commonly found modifications in epigenetics. Runt-related transcription factor 3 (RUNX3) is associated with pulmonary epithelial and vascular development and regulates expression at the post-transcriptional level by DNA methylation through DNMT1 or DNMT3b. However, the involvements of these epigenetic factors in the occurrence of BPD are, as yet, unclear. Newborn rats were randomly assigned to a model, hyperoxia (85 % O2) or control, normoxia group (21 % O2). Lung tissues and alveolar type 2 (AT2) epithelial cells were collected between 1-14 days. The expression of DNMTs, and EZH2 was detected by immunohistochemistry, Western blot and real-time PCR. The percentage of DNA methylation and H3K27me3 levels in the RUNX3 promoter region was measured by bisulfite sequencing PCR and chromatin immunoprecipitation assay. RUNX3 protein and mRNA expression in AT2 cells was also measured after inhibition using the DNA methylation inhibitor, 5-Aza-2'-deoxycytidine, the H3K27me3 inhibitor, JMJD3, and the EZH2 inhibitor, DZNep. Compared with the control group, RUNX3 protein was downregulated and DNMT3b and EZH2 were highly expressed in lung tissues and AT2 cells of the model group (P < 0.05), while high DNA methylation and H3K27me3 modifications were present in the RUNX3 promoter region, in lung tissues of the model group (P < 0.05). Following hyperoxia in the model group, JMJD3 and DZNep significantly reversed the hyperoxia-induced down-regulation of RUNX3 expression in AT2 cells (P < 0.05), more so than 5-Aza-2'-deoxycytidine (P < 0.05). 1) DNA methylation and H3K27 trimethylation are present in the BPD model; 2) RUNX3 down-regulation is attributed to both DNMT3b-catalyzed DNA methylation and EZH2-catalyzed histone methylation.

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X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 18%
Professor > Associate Professor 3 14%
Student > Ph. D. Student 3 14%
Student > Master 2 9%
Student > Doctoral Student 1 5%
Other 1 5%
Unknown 8 36%
Readers by discipline Count As %
Medicine and Dentistry 8 36%
Biochemistry, Genetics and Molecular Biology 2 9%
Agricultural and Biological Sciences 1 5%
Neuroscience 1 5%
Engineering 1 5%
Other 0 0%
Unknown 9 41%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 July 2015.
All research outputs
#14,914,476
of 25,374,647 outputs
Outputs from Respiratory Research
#1,499
of 3,062 outputs
Outputs of similar age
#131,015
of 278,441 outputs
Outputs of similar age from Respiratory Research
#22
of 41 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,062 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 278,441 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.