Evidence map›Paper›PMID 39578365›Full record

ArticleJournal of the American Heart Association2024

Promotor Hypomethylation Mediated Upregulation of VCAN Targets Twist1 to Promote EndMT in Hypoxia-Induced Pulmonary Hypertension.

Jinyan Yu, Shanchao Hong, Lingjia Yang, Shugao Ye, Zhen Yu, Zheming Zhang, Ziteng Wang, Shulun Huang, Yuan Chen, Tao Bian and 1 more

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Jinyan YuDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.ORCID 0000-0002-1017-4341
Shanchao HongDepartment of Clinical Laboratory Jiangnan University Medical Center Wuxi Jiangsu People's Republic of China.
Lingjia YangDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.
Shugao YeTransplant Center The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.
Zhen YuDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.
Zheming ZhangDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.
Ziteng WangDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.
Shulun HuangDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.
Yuan ChenTransplant Center The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.
Tao BianDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.ORCID 0009-0005-4516-4855
Yan WuDepartment of Respiratory Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University Wuxi Jiangsu People's Republic of China.ORCID 0009-0006-2767-9297

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypoxia-induced pulmonary hypertension (HPH) is a severe vascular disorder that is characterized by the involvement of endothelial-to-mesenchymal transition (EndMT) in its pathogenesis. Our previous research has suggested that the gene versican may have a crucial role in the development of HPH. However, the exact function of versican in HPH requires further investigation. METHODS AND

resultsThe expression of versican and markers of EndMT was assessed using Western blot, immunohistochemistry, and immunofluorescence. Vascular remodeling and right ventricular hypertrophy in patients with HPH and mice were evaluated through hematoxylin and eosin staining, Masson's staining, and hemodynamic measurements. Protein interactions were validated using co-immunoprecipitation, and the DNA methylation level of versican was examined using methylation-specific polymerase chain reaction. Compared with the control, EndMT was observed in patients with HPH, HPH mouse models, and hypoxia-treated human pulmonary artery endothelial cells, accompanied by a significant increase of versican. Endothelium-specific knockdown of versican reversed HPH progression and effectively prevented EndMT in mouse models and human pulmonary artery endothelial cells. We further confirmed that versican participated in EndMT by targeting the key transcription factor Twist1. Additionally, the upregulation of versican may be attributed to promoter hypomethylation, which was mediated by reduced DNA methyltransferases activity under hypoxic conditions.

conclusionsThis study provides the initial evidence showcasing the role of promoter hypomethylation-mediated versican upregulation in promoting EndMT by targeting Twist1, which facilitates vascular remodeling and the progression of HPH. These findings offer a promising new target for the treatment of HPH.

Indexed as

Disease Models, AnimalDNA MethylationEpithelial-Mesenchymal TransitionHypertension, PulmonaryHypoxiaNuclear ProteinsPromoter Regions, GeneticTwist-Related Protein 1Up-RegulationVersicansAnimalsCells, CulturedEndothelial CellsEndothelial-Mesenchymal TransitionFemaleHumansNuclear ProteinsTWIST1 protein, humanTwist1 protein, mouseTwist-Related Protein 1VCAN protein, humanVersicansDNA methylationendothelial‐to‐mesenchymal transitionhypoxia‐induced pulmonary hypertensionTwist1versican

Identifiers

PMID39578365
PMCPMC11681555

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.