Evidence map›Paper›PMID 22705205›Full record

ArticleBiochimica et biophysica acta2012

TGF-β inhibits the uptake of modified low density lipoprotein by human macrophages through a Smad-dependent pathway: a dominant role for Smad-2.

Daryn R Michael, Rebecca C Salter, Dipak P Ramji

Open access · hybridAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
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  10. Dihomo-γ-linolenic acid inhibits several key cellular processes associated with atherosclerosis.Biochimica et biophysica acta. Molecular basis of disease · 2019
    Article
  11. Article
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  13. Fatty Acid Metabolism, Bone Morphogenetic Protein Receptor Type 2, and the Right Ventricle.American journal of respiratory and critical care medicine · 2016
    Article
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  15. Review
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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

3 authors at 1 institution in 1 country.

Daryn R MichaelCardiff School of Biosciences, Cardiff University, Cardiff, UK. MichaelDr1@cf.ac.uk
Rebecca C Salter
Dipak P Ramji
Cardiff University · GB

Funding

British Heart Foundation PG/08/073/25520
6 · The paper itself

Abstract

The anti-atherogenic cytokine, TGF-β, plays a key role during macrophage foam cell formation by modulating the expression of key genes involved in the control of cholesterol homeostasis. Unfortunately, the molecular mechanisms underlying these actions of TGF-β remain poorly understood. In this study we examine the effect of TGF-β on macrophage cholesterol homeostasis and delineate the role of Smads-2 and -3 during this process. Western blot analysis showed that TGF-β induces a rapid phosphorylation-dependent activation of Smad-2 and -3 in THP-1 and primary human monocyte-derived macrophages. Small interfering RNA-mediated knockdown of Smad-2/3 expression showed that the TGF-β-mediated regulation of key genes implicated in the uptake of modified low density lipoproteins and the efflux of cholesterol from foam cells was Smad-dependent. Additionally, through the use of virally delivered Smad-2 and/or Smad-3 short hairpin RNA, we demonstrate that TGF-β inhibits the uptake of modified LDL by macrophages through a Smad-dependent mechanism and that the TGF-β-mediated regulation of CD36, lipoprotein lipase and scavenger receptor-A gene expression was dependent on Smad-2. These studies reveal a crucial role for Smad signaling, particularly Smad-2, in the inhibition of foam cell formation by TGF-β through the regulation of expression of key genes involved in the control of macrophage cholesterol homeostasis.

Indexed as

CD36 AntigensCells, CulturedCholesterolFoam CellsGene ExpressionHomeostasisHumansLipoprotein LipaseLipoproteins, LDLMacrophagesPhosphorylationScavenger Receptors, Class ASignal TransductionSmad2 ProteinSmad3 ProteinTransforming Growth Factor betaCD36 AntigensCholesterolLipoprotein LipaseLipoproteins, LDLScavenger Receptors, Class ASmad2 ProteinSMAD2 protein, humanSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor beta

Identifiers

PMID22705205
PMCPMC3497875
OpenAlexW2153590662

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.