Evidence map›Paper›PMID 24590289›Full record

ArticleThe Journal of clinical investigation2014

Fibrotic extracellular matrix activates a profibrotic positive feedback loop.

Matthew W Parker, Daniel Rossi, Mark Peterson, Karen Smith, Kristina Sikström, Eric S White, John E Connett, Craig A Henke, Ola Larsson, Peter B Bitterman

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 337 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
337citing papers in PubMed, 2 pooled it
33.8field-weighted citation impact, top 1% 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

337 citing papers in PubMed, 2 syntheses or guidelines pooled it, 539 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026
    Review
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  7. Association ofInternational journal of molecular sciences · 2026
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277 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 2 countries.

Matthew W Parker
Daniel Rossi
Mark Peterson
Karen Smith
Kristina Sikström
Eric S White
John E Connett
Craig A Henke
Ola Larsson
Peter B Bitterman
University of Minnesota · USKarolinska Institutet · SEPulmonary and Allergy Associates · USTwin Cities Orthopedics · USPulmonary and Critical Care Associates · US

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
Translational control of the fibroblast phenotype in IPFP01HL091775 · NHLBI · UNIVERSITY OF MINNESOTA · PI INGBAR, DAVID H · 2009 to 2013
$8.3M
Matrix and Bioreactors for Human Lung RegenerationU01HL111016 · NHLBI · YALE UNIVERSITY · PI NIKLASON, LAURA E, WHITE, ERIC S · 2012 to 2016
$3.2M
Role of fibrotic extracellular matrix in generating the IPF FibroblastR01HL125236 · NHLBI · UNIVERSITY OF MINNESOTA · PI BITTERMAN, PETER B · 2015 to 2018
$1.9M
Role of EIIIA fibronectin in pulmonary fibrosisR01HL085083 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WHITE, ERIC S · 2007 to 2011
$1.9M
Translational Control in IPFR01HL089249 · NHLBI · UNIVERSITY OF MINNESOTA · PI BITTERMAN, PETER B · 2008 to 2011
$1.8M
Genome-Wide Analysis of Matrix Driven Pathological Translational Control in IPFF32HL116105 · NHLBI · UNIVERSITY OF MINNESOTA · PI PARKER, MATTHEW W · 2013 to 2013
$46k
NCATS NIH HHS UL1 TR000114NHLBI NIH HHS F32 HL116105NHLBI NIH HHS P01 HL091775NHLBI NIH HHS P01 HL91775NHLBI NIH HHS R01 HL085083NHLBI NIH HHS R01 HL089249NHLBI NIH HHS R01 HL125236NHLBI NIH HHS U01 HL111016
6 · The paper itself

Abstract

Pathological remodeling of the extracellular matrix (ECM) by fibroblasts leads to organ failure. Development of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive fibrotic scarring in the lung that ultimately leads to asphyxiation; however, the cascade of events that promote IPF are not well defined. Here, we examined how the interplay between the ECM and fibroblasts affects both the transcriptome and translatome by culturing primary fibroblasts generated from IPF patient lung tissue or nonfibrotic lung tissue on decellularized lung ECM from either IPF or control patients. Surprisingly, the origin of the ECM had a greater impact on gene expression than did cell origin, and differences in translational control were more prominent than alterations in transcriptional regulation. Strikingly, genes that were translationally activated by IPF-derived ECM were enriched for those encoding ECM proteins detected in IPF tissue. We determined that genes encoding IPF-associated ECM proteins are targets for miR-29, which was downregulated in fibroblasts grown on IPF-derived ECM, and baseline expression of ECM targets could be restored by overexpression of miR-29. Our data support a model in which fibroblasts are activated to pathologically remodel the ECM in IPF via a positive feedback loop between fibroblasts and aberrant ECM. Interrupting this loop may be a strategy for IPF treatment.

Indexed as

AgedCase-Control StudiesCell LineExtracellular MatrixExtracellular Matrix ProteinsFeedback, PhysiologicalFibroblastsGene ExpressionHumansIdiopathic Pulmonary FibrosisMicroRNAsMiddle AgedModels, BiologicalProtein BiosynthesisExtracellular Matrix ProteinsMicroRNAsMIRN29a microRNA, human

Identifiers

PMID24590289
PMCPMC3971953
OpenAlexW2116043657

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.