Evidence map›Paper›PMID 34753038›Full record

ArticleBiomaterials2021

A Src-H3 acetylation signaling axis integrates macrophage mechanosensation with inflammatory response.

Praveen Krishna Veerasubramanian, Hanjuan Shao, Vijaykumar S Meli, Tri Andrew Q Phan, Thuy U Luu, Wendy F Liu, Timothy L Downing

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

Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% 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, 1 synthesis or guideline pooled it, 25 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

7 authors at 1 institution in 1 country.

Praveen Krishna VeerasubramanianDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, CA, USA.
Hanjuan ShaoDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, CA, USA.
Vijaykumar S MeliDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, CA, USA.
Tri Andrew Q PhanDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, CA, USA.
Thuy U LuuUCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, CA, USA; Department of Pharmacological Sciences, University of California Irvine, Irvine, CA, USA.
Wendy F LiuDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, CA, USA; Department of Chemical and Biomolecular Engineering, University of California Irvine, Irvine, CA, USA; Institute for Immunology, University of California Irvine, Irvine, CA, USA; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA.
Timothy L DowningDepartment of Biomedical Engineering, University of California Irvine, Irvine, CA, USA; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California Irvine, Irvine, CA, USA; NSF-Simons Center for Multiscale Cell Fate Research, University of California Irvine, Irvine, CA, USA; Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, CA, USA. Electronic address: tim.downing@uci.edu.
University of California, Irvine · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Uncover Strategies Used By Biological SystemsP50GM076516 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI NIE, QING · 2007 to 2016
$25.1M
Biophysical regulation of macrophage functionR01AI151301 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, WENDY · 2020 to 2024
$2.9M
Spatial epigenomics: A new framework for overcoming mechanical heterogeneity in solid tumorsDP2CA250382 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI DOWNING, TIMOTHY LAMONT · 2019 to 2019
$2.4M
Training Program in Cardiovascular Applied Research and EntrepreneurshipT32HL116270 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUGHES, CHRISTOPHER C. W. · 2013 to 2022
$1.6M
Multiphoton Microscope for Cardiovascular and Tissue EngineeringS10OD025064 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI BOTVINICK, ELLIOT LAWRENCE · 2019 to 2019
$595k
Mechanochemical regulation of macrophages by the extracellular matrix during wound healingR21AI128519 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, WENDY · 2017 to 2018
$405k
Epigenetic regulation of macrophage response to biomaterial implantsR21EB027840 · NIBIB · UNIVERSITY OF CALIFORNIA-IRVINE · PI DOWNING, TIMOTHY LAMONT, LIU, WENDY · 2019 to 2020
$398k
NCATS NIH HHS UL1 TR001414NCI NIH HHS DP2 CA250382NCI NIH HHS P30 CA062203NHLBI NIH HHS T32 HL116270NIAID NIH HHS R01 AI151301NIAID NIH HHS R21 AI128519NIBIB NIH HHS R21 EB027840NIGMS NIH HHS P50 GM076516NIH HHS S10 OD025064
6 · The paper itself

Abstract

Macrophages are mechanosensitive cells that can exquisitely fine-tune their function in response to their microenvironment. While macrophage polarization results in concomitant changes in cell morphology and epigenetic reprogramming, how biophysically-induced signaling cascades contribute to gene regulatory programs that drive polarization remains unknown. We reveal a cytoskeleton-dependent Src-H3 acetylation (H3Ac) axis responsible for inflammation-associated histone hyperacetylation. Inflammatory stimuli caused increases in traction forces, Src activity and H3Ac marks in macrophages, accompanied by reduced cell elongation and motility. These effects were curtailed following disruption of H3Ac-signaling through either micropattern-induced cell elongation or inhibition of H3Ac readers (BRD proteins) directly. Src activation relieves the suppression of p300 histone acetyltransferase (HAT) activity by PKCδ. Furthermore, while inhibition of Src reduced p300 HAT activity and H3Ac marks globally, local H3Ac levels within the Src promoter were increased, suggesting H3Ac regulates Src levels through feedback. Together, our study reveals an adhesome-to-epigenome regulatory nexus underlying macrophage mechanosensation, where Src modulates H3Ac-associated epigenetic signaling as a means of tuning inflammatory gene activity and macrophage fate decisions in response to microenvironmental cues.

Indexed as

Histone AcetyltransferasesHistonesAcetylationMacrophagesSignal TransductionHistone AcetyltransferasesHistonesBiophysical cuesEpigenetic regulationInflammationMacrophagesSrc-kinase signaling

Identifiers

PMID34753038
PMCPMC8939266
OpenAlexW3208041731

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.