Evidence map›Paper›PMID 24403604›Full record

ArticleMolecular biology of the cell2014

Functional genomic screen identifies novel mediators of collagen uptake.

Ting-Hein Lee, William McKleroy, Amin Khalifeh-Soltani, Stephen Sakuma, Stanislav Lazarev, Kirsi Riento, Stephen L Nishimura, Ben J Nichols, Kamran Atabai

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2014. 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
1.4field-weighted citation impact, top 21% 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, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. You Say You Want a Resolution (of Fibrosis).American journal of respiratory cell and molecular biology · 2020
    Review
  6. Article
  7. Flotillin membrane domains in cancer.Cancer metastasis reviews · 2020
    Review
  8. Article
  9. Mechanisms for the Resolution of Organ Fibrosis.Physiology (Bethesda, Md.) · 2019
    Review
  10. Article
  11. Extracellular matrix in lung development, homeostasis and disease.Matrix biology : journal of the International Society for Matrix Biology · 2018
    Review
  12. Matrix biomechanics and dynamics in pulmonary fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2018
    Review
  13. Cell division cycle 7 kinase is a negative regulator of cell-mediated collagen degradation.American journal of physiology. Lung cellular and molecular physiology · 2018
    Article
  14. Article
  15. Matrix, mesenchyme, and mechanotransduction.Annals of the American Thoracic Society · 2015
    Review
  16. Article
  17. Fibrocytes are not an essential source of type I collagen during lung fibrosis.Journal of immunology (Baltimore, Md. : 1950) · 2014
    Article
  18. Article
  19. Integrating omics technologies to study pulmonary physiology and pathology at the systems level.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2014
    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

9 authors at 2 institutions in 2 countries.

Ting-Hein LeeCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158 Department of Medicine, University of California, San Francisco, San Francisco, CA 94158 Lung Biology Center, University of California, San Francisco, San Francisco, CA 94158 Department of Pathology, University of California, San Francisco, San Francisco, CA 94158 MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
William McKleroy
Amin Khalifeh-Soltani
Stephen Sakuma
Stanislav Lazarev
Kirsi Riento
Stephen L Nishimura
Ben J Nichols
Kamran Atabai
University of California, San Francisco · USMRC Laboratory of Molecular Biology · GB

Funding

Integrin avB8 Inhibits Airway Epithelial Cell GrowthR01HL063993 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2001 to 2011
$3.3M
Role of genetic variation in TGF-beta overactivation in COPDR01HL113032 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2012 to 2015
$2.1M
The Role of Collagen Uptake in Regulating the Severity of Pulmonary FibrosisR01HL104009 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ATABAI, KAMRAN · 2011 to 2015
$1.9M
Identification of Pathways that Regulate Fibrosis through Collagen ResorptionR21HL107972 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ATABAI, KAMRAN · 2011 to 2012
$425k
Medical Research Council MC_U105178778NHLBI NIH HHS HL063993NHLBI NIH HHS HL104009NHLBI NIH HHS HL107972NHLBI NIH HHS HL113032NHLBI NIH HHS R01 HL063993NHLBI NIH HHS R01 HL104009NHLBI NIH HHS R01 HL113032NHLBI NIH HHS R21 HL107972
6 · The paper itself

Abstract

Tissue fibrosis occurs when matrix production outpaces matrix degradation. Degradation of collagen, the main component of fibrotic tissue, is mediated through an extracellular proteolytic pathway and intracellular pathway of cellular uptake and lysosomal digestion. Recent studies demonstrate that disruption of the intracellular pathways can exacerbate fibrosis. These pathways are poorly characterized. Here we identify novel mediators of the intracellular pathway of collagen turnover through a genome-wide RNA interference screen in Drosophila S2 cells. Screening of 7505 Drosophila genes conserved among metazoans identified 22 genes that were required for efficient internalization of type I collagen. These included proteins involved in vesicle transport, the actin cytoskeleton, and signal transduction. We show further that the flotillin genes have a conserved and central role in collagen uptake in Drosophila and human cells. Short hairpin RNA-mediated silencing of flotillins in human monocyte and fibroblasts impaired collagen uptake by promoting lysosomal degradation of the endocytic collagen receptors uPARAP/Endo180 and mannose receptor. These data provide an initial characterization of intracellular pathways of collagen turnover and identify the flotillin genes as critical regulators of this process. A better understanding of these pathways may lead to novel therapies that reduce fibrosis by increasing collagen turnover.

Indexed as

AnimalsCollagenDrosophilaDrosophila ProteinsGene Knockdown TechniquesGenome, InsectHumansMembrane ProteinsRNA InterferenceCollagenDrosophila ProteinsflotillinsMembrane Proteins

Identifiers

PMID24403604
PMCPMC3937085
OpenAlexW2127197216

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.