Evidence map›Paper›PMID 16258061›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2005

Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia.

Jackie G Lee, Sia Dahi, Rajeev Mahimkar, Nathaniel L Tulloch, Maria A Alfonso-Jaume, David H Lovett, Rajabrata Sarkar

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.1field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
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  6. Heat shock protein 90 inhibition by 17-DMAG attenuates abdominal aortic aneurysm formation in mice.American journal of physiology. Heart and circulatory physiology · 2015
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  16. Matrix metalloproteinase control of capillary morphogenesis.Critical reviews in eukaryotic gene expression · 2008
    Review
  17. Article
  18. Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic beta-cells.Proceedings of the National Academy of Sciences of the United States of America · 2007
    Article
  19. Article
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

7 authors at 2 institutions in 1 country.

Jackie G LeeDivision of Vascular Surgery, San Francisco Veterans Affairs Medical Center, and Pacific Vascular Research Laboratory, University of California, San Francisco, CA 94121, USA.
Sia Dahi
Rajeev Mahimkar
Nathaniel L Tulloch
Maria A Alfonso-Jaume
David H Lovett
Rajabrata Sarkar
University of California, San Francisco · USSan Francisco VA Medical Center · US

Funding

Mechanisms of Cardioprotection in Ischemia and FailureP01HL068738 · NHLBI · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI KARLINER, JOEL SAMUEL · 2002 to 2006
$8.6M
NITRIC OXIDE AND SMOOTH MUSCLE CELL PROLIFERATIONK08HL004435 · NHLBI · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI SARKAR, RAJABRATA · 2000 to 2004
$649k
NHLBI NIH HHS K08 HL004435NHLBI NIH HHS P01 HL068738NHLBI NIH HHS P01 HL 68738
6 · The paper itself

Abstract

Matrix metalloproteinase-2 (MMP-2) plays an essential role in angiogenesis and arteriogenesis, two processes critical to restoration of tissue perfusion after ischemia. MMP-2 expression is increased in tissue ischemia, but the responsible mechanisms remain unknown. We studied the transcriptional activation of the MMP-2 gene in a model of hindlimb ischemia by using various MMP-2-lacZ reporter mice and chromatin immunoprecipitation. MMP-2 activity and mRNA were increased after hindlimb ischemia. Mice with targeted deletion of MMP-2 had impaired restoration of perfusion and a high incidence of limb gangrene, indicating that MMP-2 plays a critical role in ischemia-induced revascularization. Ischemia induced the expression and binding of c-Fos, c-Jun, JunB, FosB, and Fra2 to a noncanonical activating protein-1 (AP-1) site present in the MMP-2 promoter and decreased binding of the transcriptional repressor JunD. Ischemia also activated the expression and binding of p53 to an adjacent enhancer site (RE-1) and increased expression and binding of nuclear factor of activated T-cells-c2 to consensus sequences within the first intron. Deletion of either the 5' AP-1/RE-1 region of the promoter or substitution of the first intron abolished ischemia-induced MMP-2 transcription in vivo. Thus, AP-1 transcription factors and intronic activation by nuclear factor of activated T-cells-c2 act in concert to drive ischemia-induced MMP-2 transcription. These findings define a critical role for MMP-2 in ischemia-induced revascularization and identify both previously uncharacterized regulatory elements within the MMP-2 gene and the cognate transcription factors required for MMP-2 activation in vivo after tissue ischemia.

Indexed as

IntronsTranscription, GeneticAnimalsEnhancer Elements, GeneticHindlimbIschemiaMatrix Metalloproteinase 2MiceMice, Inbred C57BLMuscle, SkeletalNFATC Transcription FactorsPromoter Regions, GeneticTranscription Factor AP-1Tumor Suppressor Protein p53Matrix Metalloproteinase 2Nfatc2 protein, mouseNFATC Transcription FactorsTranscription Factor AP-1Tumor Suppressor Protein p53

Identifiers

PMID16258061
PMCPMC1283457
OpenAlexW2057448298

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.