Evidence map›Paper›PMID 39418109›Full record

ArticleJCI insight2024

Inhibiting triggering receptor expressed on myeloid cells 1 signaling to ameliorate skin fibrosis.

Swarna Bale, Priyanka Verma, Bharath Yalavarthi, Matija Bajželj, Syed Am Hasan, Jenna N Silverman, Katherine Broderick, Kris A Shah, Timothy Hamill, Dinesh Khanna and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
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

13 authors.

Swarna BaleMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Priyanka VermaMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Bharath YalavarthiMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Matija BajželjMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Syed Am HasanMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Jenna N SilvermanMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Katherine BroderickMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Kris A ShahMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Timothy HamillMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Dinesh KhannaMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Alexander B SigalovSignaBlok Inc., Shrewsbury, Massachusetts, USA.
Swati BhattacharyyaMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
John VargaMichigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Funding

Damage-Associated Molecular Patterns Driving Fibrosis Progression in SclerodermaR01AR074997 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VARGA, JOHN · 2019 to 2023
$2.3M
TREM-1 inhibitor for the treatment of sclerodermaR43AR078110 · NIAMS · SIGNABLOK, INC. · PI SIGALOV, ALEXANDER B · 2020 to 2020
$250k
NIAMS NIH HHS R01 AR074997NIAMS NIH HHS R43 AR078110
6 · The paper itself

Abstract

Systemic sclerosis (SSc) is characterized by immune system failure, vascular insult, autoimmunity, and tissue fibrosis. TGF-β is a crucial mediator of persistent myofibroblast activation and aberrant extracellular matrix production in SSc. The factors responsible for this are unknown. By amplifying pattern recognition receptor signaling, triggering receptor expressed on myeloid cells 1 (TREM-1) is implicated in multiple inflammatory conditions. In this study, we used potentially novel ligand-independent TREM-1 inhibitors in preclinical models of fibrosis and explanted SSc skin fibroblasts in order to investigate the pathogenic role of TREM-1 in SSc. Selective pharmacological TREM-1 blockade prevented and reversed skin fibrosis induced by bleomycin in mice and mitigated constitutive collagen synthesis and myofibroblast features in SSc fibroblasts in vitro. Our results implicate aberrantly activated TREM-1 signaling in SSc pathogenesis, identify a unique approach to TREM-1 blockade, and suggest a potential therapeutic benefit for TREM-1 inhibition.

Indexed as

BleomycinFibroblastsFibrosisScleroderma, SystemicSignal TransductionSkinTriggering Receptor Expressed on Myeloid Cells-1AnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMyofibroblastsBleomycinTREM1 protein, mouseTriggering Receptor Expressed on Myeloid Cells-1Autoimmune diseasesAutoimmunityInfectious diseaseRheumatology

Identifiers

PMID39418109
PMCPMC11623937

What Socratic 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 Socratic graph.