Evidence map›Paper›PMID 38493137›Full record

ArticleCell communication and signaling : CCS2024

Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.

Alexander Bigger-Allen, Ali Hashemi Gheinani, Rosalyn M Adam

Open access · goldAbstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Alexander Bigger-AllenUrological Diseases Research Center, Boston Children's Hospital, Enders Bldg 1061.4, 300 Longwood Avenue, Boston, MA, 02115, USA.
Ali Hashemi GheinaniUrological Diseases Research Center, Boston Children's Hospital, Enders Bldg 1061.4, 300 Longwood Avenue, Boston, MA, 02115, USA.
Rosalyn M AdamUrological Diseases Research Center, Boston Children's Hospital, Enders Bldg 1061.4, 300 Longwood Avenue, Boston, MA, 02115, USA. rosalyn.adam@childrens.harvard.edu.
Boston Children's Hospital · USHarvard University · US

Funding

MECHANOTRANSDUCTION IN BLADDER SMOOTH MUSCLER01DK077195 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ADAM, ROSALYN M · 2008 to 2018
$3.4M
NIMBLE: Non-Invasive Markers of Bladder DeteriorationR01DK127673 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ADAM, ROSALYN M, LEE, RICHARD SANG-YONG · 2021 to 2025
$2.8M
The neuropilin 2 axis in smooth muscle contractilityR01DK104641 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ADAM, ROSALYN M, BIELENBERG, DIANE RENEE · 2016 to 2020
$2.4M
NIDDK NIH HHS DK077195NIDDK NIH HHS R01 DK077195NIDDK NIH HHS R01 DK104641NIDDK NIH HHS R01 DK127673
6 · The paper itself

Abstract

backgroundInjury to contractile organs such as the heart, vasculature, urinary bladder and gut can stimulate a pathological response that results in loss of normal contractility. PDGF and TGFβ are among the most well studied initiators of the injury response and have been shown to induce aberrant contraction in mechanically active cells of hollow organs including smooth muscle cells (SMC) and fibroblasts. However, the mechanisms driving contractile alterations downstream of PDGF and TGFβ in SMC and fibroblasts are incompletely understood, limiting therapeutic interventions.

methodsTo identify potential molecular targets, we have leveraged the analysis of publicly available data, comparing transcriptomic changes in mechanically active cells stimulated with PDGF and TGFβ. Additional Analysis of publicly available data sets were performed on SMC and fibroblasts treated in the presence or absence of the MYC inhibitor JQ1. Validation of in silico findings were performed with qPCR, immunoblots, and collagen gel contraction assays measure the effect of JQ1 on cytoskeleton associated genes, proteins and contractility in mechanically active cells. Likelihood ratio test and FDR adjusted p-values were used to determine significant differentially expressed genes. Student ttest were used to calculate statistical significance of qPCR and contractility analyses.

resultsComparing PDGF and TGFβ stimulated SMC and fibroblasts identified a shared molecular profile regulated by MYC and members of the AP-1 transcription factor complex. Additional in silico analysis revealed a unique set of cytoskeleton-associated genes that were sensitive to MYC inhibition with JQ1. In vitro validation demonstrated JQ1 was also able to attenuate TGFβ and PDGF induced changes to the cytoskeleton and contraction of smooth muscle cells and fibroblasts in vitro.

conclusionsThese findings identify MYC as a key driver of aberrant cytoskeletal and contractile changes in fibroblasts and SMC, and suggest that JQ1 could be used to restore normal contractile function in hollow organs.

Indexed as

Nuclear ProteinsTranscription FactorsCells, CulturedCytoskeletonHumansMyocytes, Smooth MuscleTransforming Growth Factor betaNuclear ProteinsTranscription FactorsTransforming Growth Factor betaFibroblastsJQ1MycPDGFSmooth muscle cellsTGFβ

Identifiers

PMID38493137
PMCPMC10944605
OpenAlexW4392878645

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.