Evidence map›Paper›PMID 39195221›Full record

ArticleCells2024

Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling.

Huynh Van Tin, Lekha Rethi, Satoshi Higa, Yu-Hsun Kao, Yi-Jen Chen

Abstract read
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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.

Huynh Van TinInternational Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Lekha RethiDepartment of Orthopedics, Shuangho Hospital, Taipei Medical University, Taipei 11031, Taiwan.
Satoshi HigaCardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa 901-2131, Japan.ORCID 0000-0002-5735-6249
Yu-Hsun KaoInternational Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.ORCID 0000-0001-8687-5091
Yi-Jen ChenInternational Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.ORCID 0000-0001-7224-4491

Funding

National Science and Technology Council 110-2314-B-038-128Wan Fang Hospital 113-wf-eva-12
6 · The paper itself

Abstract

backgroundThe spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to viral entry and can cause cardiac injuries. Toll-like receptor 4 (TLR4) and NOD-, LPR-, and pyrin-domain-containing 3 (NLRP3) inflammasome are critical immune system components implicated in cardiac fibrosis. The spike protein activates NLRP3 inflammasome through TLR4 or angiotensin-converting enzyme 2 (ACE2) receptors, damaging various organs. However, the role of spike protein in cardiac fibrosis in humans, as well as its interactions with NLRP3 inflammasomes and TLR4, remain poorly understood.

methodsWe utilized scratch assays, Western blotting, and immunofluorescence to evaluate the migration, fibrosis signaling, mitochondrial calcium levels, reactive oxygen species (ROS) production, and cell morphology of cultured human cardiac fibroblasts (CFs) treated with spike (S1) protein for 24 h with or without an anti-ACE2 neutralizing antibody, a TLR4 blocker, or an NLRP3 inhibitor.

resultsS1 protein enhanced CFs migration and the expressions of collagen 1, α-smooth muscle actin, transforming growth factor β1 (TGF-β1), phosphorylated SMAD2/3, interleukin 1β (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). S1 protein increased ROS production but did not affect mitochondrial calcium content and cell morphology. Treatment with an anti-ACE2 neutralizing antibody attenuated the effects of S1 protein on collagen 1 and TGF-β1 expressions. Moreover, NLRP3 (MCC950) and NF-kB inhibitors, but not the TLR4 inhibitor TAK-242, prevented the S1 protein-enhanced CFs migration and overexpression of collagen 1, TGF-β1, and IL-1β.

conclusionS1 protein activates human CFs by priming NLRP3 inflammasomes through NF-κB signaling in an ACE2-dependent manner.

Indexed as

FibrosisInflammasomesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinSARS-CoV-2Signal TransductionSpike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Cell MovementCells, CulturedCOVID-19FibroblastsHumansMyocardiumReactive Oxygen SpeciesToll-Like Receptor 4Angiotensin-Converting Enzyme 2InflammasomesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanReactive Oxygen SpeciesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Toll-Like Receptor 4angiotensin-converting enzyme 2cardiac fibroblastsNLRP3 inflammasomespike protein

Identifiers

PMID39195221
PMCPMC11353017

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.