ArticleCell death and differentiation2020
FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 3 of them syntheses that pooled 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.
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.
Who cites it
229 citing papers in PubMed, 3 syntheses or guidelines pooled it, 440 citations in OpenAlex.
- The Role of mTOR in the Doxorubicin-Induced Cardiotoxicity: A Systematic Review.Cell biochemistry and biophysics · 2025Pooled it
- Organokines in COVID-19: A Systematic Review.Cells · 2023Pooled it
- Mapping current research and identifying hotspots of ferroptosis in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- HydroMg attenuates doxorubicin-induced myocardial injury via promoting mitochondrial function.Medical gas research · 2027Article
- FNDC5-overexpressed BMSCs attenuated brachial plexus root avulsion by enhancing BMSCs survival and inhibiting motoneurons apoptosis.IBRO neuroscience reports · 2026Article
- Vardenafil Alleviates Doxorubicin-Induced Cardiotoxicity Associated with Restoration of the AMPK/SIRT1 Signaling Pathway.Biomedicines · 2026Article
- Autophagic therapeutic targeting for Doxorubicin-induced cardiomyopathy.Molecular biology reports · 2026Review
- Endothelial progenitor cell susceptibility to DNA damaging and DDR-modulating compounds determines endothelial differentiation accuracy.Stem cell research & therapy · 2026Article
- Arachidonate lipoxygenase 5 metabolism axis promoting ferroptosis: a potential druggable target for doxorubicin-induced cardiomyopathy.British journal of cancer · 2026Article
- KLF9 Aggravates Doxorubicin-Induced Cardiotoxicity by Regulating the ROS/p53 Signalling Pathway.Cardiovascular toxicology · 2026Article
- Protective effects of irisin in sarcopenia: a promising treatment.Journal of orthopaedic translation · 2026Review
- VSNL1 attenuates hypoxia‑induced myocardial apoptosis by regulating the CNP/NPRB pathway.Molecular medicine reports · 2026Article
- Cardiac reprogramming via transient overexpression of P-glycoprotein alleviates doxorubicin-induced cardiotoxicity in mice and pigs.Nature communications · 2026Article
- Chiral metal nanozyme-enabled SOD2 activation and siRNA delivery cooperatively mitigating chronic heart failure.Bioactive materials · 2026Article
- Lactylation at lysine 145 fosters KAT8-TIP60 complex formation to promote p53 acetylation at lysine 120 and its pro-apoptotic function.Nature communications · 2026Article
- TAX1BP1 protects against doxorubicin-induced cardiotoxicity via maintaining mitochondrial function in a mTORC2-SGK1-VDAC1 manner.Molecular medicine (Cambridge, Mass.) · 2026Article
- Fumarate hydratase ameliorates pressure overload induced cardiac remodeling by controlling Elovl7-mediated biosynthesis of unsaturated fatty acids.Acta pharmacologica Sinica · 2026Article
- Hyperoside Inhibits Doxorubicin-Induced Ferroptosis in Cardiomyocytes via the Nrf2/GPX4 Pathway.Journal of cardiovascular translational research · 2026Article
- GBVAM as a Novel NHE1 Inhibitor Alleviates Doxorubicin-Induced Cardiotoxicity via PI3K/Akt/mTOR Pathway.Drug design, development and therapy · 2026Article
- Molecular insights into irisin's role in the regulation of programmed cell death: mechanisms and therapeutic potential.Journal of molecular medicine (Berlin, Germany) · 2025Review
169 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress and cardiomyocyte apoptosis play critical roles in doxorubicin (DOX)-induced cardiotoxicity. Previous studies indicated that fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis, however, its role in DOX-induced cardiotoxicity remains unknown. Our present study aimed to investigate the role and underlying mechanism of FNDC5 on oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. Herein, we found that FNDC5 expression was downregulated in DOX-treated murine hearts and cardiomyocytes. Fndc5 deficiency resulted in increased oxidative damage and apoptosis in H9C2 cells under basal conditions, imitating the phenotype of DOX-induced cardiomyopathy in vitro, conversely, FNDC5 overexpression or irisin treatment alleviated DOX-induced oxidative stress and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, we identified that FNDC5/Irisin activated AKT/mTOR signaling and decreased DOX-induced cardiomyocyte apoptosis, and moreover, we provided direct evidence that the anti-oxidant effect of FNDC5/Irisin was mediated by the AKT/GSK3β/FYN/Nrf2 axis in an mTOR-independent manner. And we also demonstrated that heat shock protein 20 was responsible for the activation of AKT caused by FNDC5/Irisin. In line with the data in acute model, we also found that FNDC5/Irisin exerted beneficial effects in chronic model of DOX-induced cardiotoxicity (5 mg/kg, i.p., once a week for three times, the total cumulative dose is 15 mg/kg) in mice. Based on these findings, we supposed that FNDC5/Irisin was a potential therapeutic agent against DOX-induced cardiotoxicity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.