Evidence map›Paper›PMID 17478756›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2007

TNF-alpha suppresses prolyl-4-hydroxylase alpha1 expression via the ASK1-JNK-NonO pathway.

Cheng Zhang, Ming-Xiang Zhang, Ying H Shen, Jared K Burks, Yun Zhang, Jian Wang, Scott A LeMaire, Koichi Yoshimura, Hiroki Aoki, Joseph S Coselli and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
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

21 citing papers in PubMed, 44 citations in OpenAlex.

  1. Collagen Prolyl 4-Hydroxylase: An Emerging Key Player in Cardiac Fibrosis.Journal of cardiovascular translational research · 2026
    Review
  2. Review
  3. Review
  4. Effects of Mechanical Stress on Endothelial Cells In Situ and In Vitro.International journal of molecular sciences · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Therapeutic targets in the ASK1-dependent stress signaling pathways.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2012
    Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Cheng ZhangDivision of Cardiovascular Surgery, Texas Heart Institute at St. Luke's Episcopal Hospital, and Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Ming-Xiang Zhang
Ying H Shen
Jared K Burks
Yun Zhang
Jian Wang
Scott A LeMaire
Koichi Yoshimura
Hiroki Aoki
Joseph S Coselli
Xing Li Wang
Shandong University · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Matrix Metalloproteinases in Thoracic Aortic DissectionK08HL080085 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI LEMAIRE, SCOTT A · 2005 to 2009
$682k
NHLBI NIH HHS K08 HL080085
6 · The paper itself

Abstract

backgroundInflammation is known to contribute to the pathogenesis of vascular diseases in which arterial wall extracellular matrix (ECM) homeostasis is disrupted. Tumor necrosis factor-alpha (TNF-alpha), a pivotal cytokine that regulates ECM metabolism by increasing degradation and decreasing production of arterial collagens, is associated with vulnerable plaques and aortic aneurysms. METHODS AND

resultsIn the current study, we showed that, when administered in doses of 1 to 100 ng/mL, TNF-alpha dose-dependently downregulated the expression of prolyl-4-hydroxylase alphaI [P4H alpha(I)]-the rate-limiting subunit for the P4H enzyme essential for procollagen hydroxylation, secretion, and deposition in primary human aortic smooth muscle cells (HASMCs). Using a progressive deletion cloning approach, we characterized the TNF-alpha-responsive element (TaRE) in the human P4H alpha(I) promoter and found that a negative regulatory region at the position of -32 to +18 bp is responsible for approximately 80% of TNF-alpha-mediated suppression. Using oligonucleotide-based transcription factor pull-down method in which proteins were resolved in 1-D gel electrophoresis and identified using LC-MS/MS, we identified the NonO protein binds this region. When NonO expression silenced with specific siRNA, we found that 70% of the TNF-alpha-mediated P4H alpha suppression was abolished, which appeared to be mediated by the ASK1-JNK pathway.

conclusionsOur findings define a novel molecular pathway for inflammation associated extracellular matrix dysregulation, which may account for atherosclerotic plaque rupture and aortic aneurysm formation. Further understanding of this pathway may facilitate development of novel therapeutics for vascular diseases.

Indexed as

AortaBlotting, WesternCells, CulturedDNA-Binding ProteinsGene Expression RegulationHumansMAP Kinase Kinase 7MAP Kinase Kinase Kinase 5Muscle, Smooth, VascularProcollagen-Proline DioxygenaseReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSensitivity and SpecificityTumor Necrosis Factor-alphaDNA-Binding ProteinsMAP Kinase Kinase 7MAP Kinase Kinase Kinase 5P4HA1 protein, humanProcollagen-Proline DioxygenaseRNA, MessengerTumor Necrosis Factor-alpha

Identifiers

PMID17478756
PMCPMC2597036
OpenAlexW2099990733

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.