Evidence map›Paper›PMID 21612641›Full record

ArticleBMC musculoskeletal disorders2011

Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's-derived fibroblasts.

Latha Satish, Phillip H Gallo, Mark E Baratz, Sandra Johnson, Sandeep Kathju

Open access · goldAbstract read
In one paragraph

Article in BMC musculoskeletal disorders, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 5% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Latha SatishCenter for Genomic Sciences, Allegheny-Singer Research Institute, Pittsburgh, PA-15212, USA. lsatish@wpahs.org
Phillip H Gallo
Mark E Baratz
Sandra Johnson
Sandeep Kathju
Allegheny-Singer Research Institute · USAllegheny General Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyofibroblasts, a derived subset of fibroblasts especially important in scar formation and wound contraction, have been found at elevated levels in affected Dupuytren's tissues. Transformation of fibroblasts to myofibroblasts is characterized by expression of alpha- smooth muscle actin (α-SMA) and increased production of extracellular matrix (ECM) components, both events of relevance to connective tissue remodeling. We propose that increasing the activation of the cyclic AMP (cAMP)/protein kinase A signaling pathway will inhibit transforming growth factor-beta1 (TGF-β1)-induced ECM synthesis and myofibroblast formation and may provide a means to blunt fibrosis.

methodsFibroblasts derived from areas of Dupuytren's contracture cord (DC), from adjacent and phenotypically normal palmar fascia (PF), and from palmar fascia from patients undergoing carpal tunnel release (CTR; CT) were treated with TGF-β1 (2 ng/ml) and/or forskolin (10 μM) (a known stimulator of cAMP). Total RNA and protein extracted was subjected to real time RT-PCR and Western blot analysis.

resultsThe basal mRNA expression levels of fibronectin- extra domain A (FN1-EDA), type I (COL1A2) and type III collagen (COL3A1), and connective tissue growth factor (CTGF) were all significantly increased in DC- and in PF-derived cells compared to CT-derived fibroblasts. The TGF-β1 stimulation of α-SMA, CTGF, COL1A2 and COL3A1 was greatly inhibited by concomitant treatment with forskolin, especially in DC-derived cells. In contrast, TGF-β1 stimulation of FN1-EDA showed similar levels of reduction with the addition of forskolin in all three cell types.

conclusionIn sum, increasing cAMP levels show potential to inhibit the formation of myofibroblasts and accumulation of ECM components. Molecular agents that increase cAMP may therefore prove useful in mitigating DC progression or recurrence.

Indexed as

ActinsAdenylyl CyclasesAnalysis of VarianceBlotting, WesternCarpal Tunnel SyndromeCase-Control StudiesCells, CulturedColforsinCollagen Type ICollagen Type IIIConnective Tissue Growth FactorCyclic AMPCyclic AMP-Dependent Protein KinasesDupuytren ContractureEnzyme ActivationEnzyme ActivatorsACTA2 protein, humanActinsAdenylyl CyclasesCCN2 protein, humanCOL3A1 protein, humanColforsinCollagen Type ICollagen Type IIIConnective Tissue Growth FactorCyclic AMPCyclic AMP-Dependent Protein KinasesEnzyme ActivatorsExtracellular Matrix ProteinsFibronectinsRecombinant ProteinsRNA, MessengerTransforming Growth Factor beta1

Identifiers

PMID21612641
PMCPMC3125251
OpenAlexW2054736808

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.