Evidence map›Paper›PMID 21889790›Full record

ArticleThrombosis research2012

Assembly of the prothrombinase complex on the surface of human foreskin fibroblasts: Implications for connective tissue growth factor.

Mario C Rico, James J Rough, Joanne M Manns, Fabiola Del Carpio-Cano, Fayez F Safadi, Satya P Kunapuli, Raul A DeLa Cadena

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Thrombosis research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 91% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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 1 institution in 1 country.

Mario C RicoDepartment of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, United States. marior@temple.edu
James J Rough
Joanne M Manns
Fabiola Del Carpio-Cano
Fayez F Safadi
Satya P Kunapuli
Raul A DeLa Cadena
Temple University · US

Funding

Training in Thrombosis, Hemostasis and Vascular BiologyT32HL007777 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 1993 to 2012
$5.2M
Functional PKC Isoforms in PlateletsR01HL093231 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 2009 to 2017
$3.6M
Functional G Protein pathways in platelet activationR01HL081322 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 2006 to 2010
$2.9M
STEP UP In Health-Related ResearchR25HL096331 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI REEVES, KATHLEEN A · 2009 to 2018
$1.1M
Training Program in Surgical OncologyT32CA103652 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI DALY, JOHN MICHAEL · 2004 to 2008
$1.1M
TUCOE For Health Disparities Research and Training (HDRTR24MD001096 · NIMHD · TEMPLE UNIV OF THE COMMONWEALTH · PI DELA CADENA, RAUL · 2004 to 2006
$1.0M
Molecular Mechanisms of the Increased Cardiovascular Risk in Rheumatoid ArthritisK01HL103197 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RICO, MARIO CESAR · 2010 to 2014
$701k
NCI NIH HHS T32 CA103652NCI NIH HHS TA32CA103652NHLBI NIH HHS K01 HL103197NHLBI NIH HHS K01HL103197NHLBI NIH HHS R01 HL081322NHLBI NIH HHS R01HL081322NHLBI NIH HHS R01 HL093231NHLBI NIH HHS R25 HL096331NHLBI NIH HHS R25HL96331NHLBI NIH HHS T32 HL007777NHLBI NIH HHS T32HL07777NIMHD NIH HHS R24 MD001096NIMHD NIH HHS R24MD001096
6 · The paper itself

Abstract

Activated factor X (FXa) and thrombin can up-regulate gene expression of connective tissue growth factor (CTGF/CCN2) on fibroblasts. Since tissue factor (TF) is expressed on these cells, we hypothesized that they may assemble the prothrombinase complex leading to CTGF/CCN2 upregulation. In addition, the effect of thrombospondin-1 (TSP1) on this reaction was evaluated. Human foreskin fibroblasts were incubated with purified factor VII (FVII), factor X (FX), factor V (FV), prothrombin and calcium in the presence and absence of TSP1. Generation of FXa and of thrombin were assessed using chromogenic substrates. SMAD pathway phosphorylation was detected via Western-blot analysis. Pre-incubation of fibroblasts with FVII led to its auto-activation by cell-surface expressed TF, which in turn in the presence of FX, FVa, prothrombin and calcium led to FXa (9.7±0.8nM) and thrombin (7.9±0.04 U/mL×10-3) generation. Addition of TSP1 significantly enhanced thrombin (23.3±0.7 U/mL×10-3) but not FXa (8.5±0.6nM) generation. FXa and thrombin generation leads to upregulation of CTGF/CCN2. TSP1 alone upregulated CTGF/CCN2, an effect mediated via activation of transforming growth factor beta (TGFβ) as shown by phosphorylation of the SMAD pathway, an event blunted by using a TGFβ receptor I inhibitor (TGFβRI). FXa- and thrombin-induced upregulation of CTGF/CCN2 was not blocked by TGFβRI. In summary, assembly of the prothrombinase complex occurs on fibroblast's surface leading to serine proteases generation, an event enhanced by TSP1 and associated with CTGF/CCN2 upregulation. These mechanisms may play an important role in human diseases associated with fibrosis.

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell LineConnective Tissue Growth FactorFactor VFactor VIIFactor XaFibroblastsForeskinGene ExpressionHumansMaleThrombinThromboplastinTransforming Growth Factor betaBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCCN2 protein, humanConnective Tissue Growth FactorFactor VFactor VIIFactor Xaprothrombinase complexSPZ1 protein, humanThrombinThromboplastinTransforming Growth Factor beta

Identifiers

PMID21889790
PMCPMC3243815
OpenAlexW2017745069

What OpenQuestion holds

Textmetadata
LicenceTDM
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.