Evidence map›Paper›PMID 22805337›Full record

ArticleJournal of cellular and molecular medicine2012

Akt- and Erk-mediated regulation of proliferation and differentiation during PDGFRβ-induced MSC self-renewal.

Borzo Gharibi, Mandeep S Ghuman, Francis J Hughes

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular and molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.

  1. Pooled it
  2. Frontiers in medicine · 2020
    Pooled it
  3. Article
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  6. Review
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  8. Review
  9. Extracellular derivatives for bone metabolism.Journal of advanced research · 2024
    Review
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1 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

3 authors at 1 institution in 1 country.

Borzo GharibiPeriodontology, Dental Institute, King's College London, London, UK.
Mandeep S Ghuman
Francis J Hughes
King's College London · GB

Funding

Department of Health 1572
6 · The paper itself

Abstract

Understanding the mechanisms that direct mesenchymal stem cell (MSC) self-renewal fate decisions is a key to most tissue regenerative approaches. The aim of this study here was to investigate the mechanisms of action of platelet-derived growth factor receptor β (PDGFRβ) signalling on MSC proliferation and differentiation. MSC were cultured and stimulated with PDGF-BB together with inhibitors of second messenger pathways. Cell proliferation was assessed using ethynyl-2'-deoxyuridine and phosphorylation status of signalling molecules assessed by Western Blots. To assess differentiation potentials, cells were transferred to adipogenic or osteogenic media, and differentiation assessed by expression of differentiation association genes by qRT-PCR, and by long-term culture assays. Our results showed that distinct pathways with opposing actions were activated by PDGF. PI3K/Akt signalling was the main contributor to MSC proliferation in response to activation of PDGFRβ. We also demonstrate a negative feedback mechanism between PI3K/Akt and PDGFR-β expression. In addition, PI3K/Akt downstream signal cascades, mTOR and its associated proteins p70S6K and 4E-BP1 were involved. These pathways induced the expression of cyclin D1, cyclin D3 and CDK6 to promote cell cycle progression and MSC proliferation. In contrast, activation of Erk by PDGFRβ signalling potently inhibited the adipocytic differentiation of MSCs by blocking PPARγ and CEBPα expression. The data suggest that PDGFRβ-induced Akt and Erk pathways regulate opposing fate decisions of proliferation and differentiation to promote MSC self-renewal. Thus, activation of multiple intracellular cascades is required for successful and sustainable MSC self-renewal strategies.

Indexed as

Cell DifferentiationMAP Kinase Signaling SystemAdaptor Proteins, Signal TransducingBecaplerminCell Cycle ProteinsCell ProliferationCells, CulturedCyclin D1Cyclin D3Cyclin-Dependent Kinase 6G1 Phase Cell Cycle CheckpointsHumansMesenchymal Stem CellsPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationAdaptor Proteins, Signal TransducingBecaplerminCCND1 protein, humanCCND3 protein, humanCDK6 protein, humanCell Cycle ProteinsCyclin D1Cyclin D3Cyclin-Dependent Kinase 6EIF4EBP1 protein, humanMTOR protein, humanPhosphatidylinositol 3-KinasesPhosphoproteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-sisReceptor, Platelet-Derived Growth Factor betaTOR Serine-Threonine Kinases

Identifiers

PMID22805337
PMCPMC4118247
OpenAlexW2030458242

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.