ArticlePloS one2019
Doxorubicin induces trans-differentiation and MMP1 expression in cardiac fibroblasts via cell death-independent pathways.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed, 36 citations in OpenAlex.
- Mechanisms of Doxorubicin-Induced Cardiac Senescence and Potential Therapeutic Strategies.Biomolecules · 2026Review
- Doxorubicin exposure leads to cardiac fibroblast dysregulation and worsens fibrotic remodeling in the pathological heart.Journal of molecular and cellular cardiology plus · 2026Article
- Co-culturing hiPSC-cardiomyocytes and cardiac fibroblasts enhances engineered heart tissue structure and function.Stem cells translational medicine · 2026Article
- Novel Protective Role for Gut Microbiota-derived Metabolite PAGln in Doxorubicin-induced Cardiotoxicity.Cardiovascular drugs and therapy · 2026Article
- Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity.Cells · 2025Review
- Cancer therapy and cachexia.The Journal of clinical investigation · 2025Review
- Prevention and treatment of anthracycline-induced cardiotoxicity: A bibliometric analysis of the years 2000-2023.Heliyon · 2024Article
- Anticancer drugs and cardiotoxicity: the role of cardiomyocyte and non-cardiomyocyte cells.Frontiers in cardiovascular medicine · 2024Review
- Initial Phase of Anthracycline Cardiotoxicity Involves Cardiac Fibroblasts Activation and Metabolic Switch.Cancers · 2023Article
- Priorities in Cardio-Oncology Basic and Translational Science: GCOS 2023 Symposium Proceedings:JACC. CardioOncology · 2023Review
- Doxorubicin-induced modulation of TGF-β signaling cascade in mouse fibroblasts: insights into cardiotoxicity mechanisms.Scientific reports · 2023Article
- Physiological functions of calcium signaling via Orai1 in cancer.The journal of physiological sciences : JPS · 2023Review
- Identification of crucial genes related to heart failure based on GEO database.BMC cardiovascular disorders · 2023Article
- Adriamycin induces cardiac fibrosis in mice via PRMT5-mediated cardiac fibroblast activation.Acta pharmacologica Sinica · 2023Article
- Risk factors from Framingham risk score for anthracyclines cardiotoxicity in breast cancer: A systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2023Article
- Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications.Frontiers in cardiovascular medicine · 2023Review
- Role of non-cardiomyocytes in anticancer drug-induced cardiotoxicity: A systematic review.iScience · 2022Review
- Cardiac fibrosis in oncologic therapies.Current opinion in physiology · 2022Article
- One-step visualization of natural cell activities in non-labeled living spheroids.Scientific reports · 2022Article
- Store-operated calcium entry via ORAI1 regulates doxorubicin-induced apoptosis and prevents cardiotoxicity in cardiac fibroblasts.PloS one · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although doxorubicin (DOX)-induced cardiomyopathy causes lethal heart failure (HF), no early detection or effective treatment methods are available. The principal mechanisms of cardiotoxicity are considered to involve oxidative stress and apoptosis of cardiomyocytes. However, the effect of DOX on cardiac fibroblasts at non-lethal concentrations remains unknown. The aim of this study was to investigate the direct effect of doxorubicin on the activation of cardiac fibroblasts independent of cell death pathways. We first found that DOX induced α-SMA expression (marker of trans-differentiation) at a low concentration range, which did not inhibit cell viability. DOX also increased MMP1, IL-6, TGF-β and collagen expression in human cardiac fibroblasts (HCFs). In addition, DOX promoted Akt and Smad phosphorylation. A Smad inhibitor prevented DOX-induced α-SMA and IL-6 protein expression. An PI3K inhibitor also prevented MMP1 mRNA expression in HCFs. These findings suggest that DOX directly induces fibrotic changes in HCFs via cell death-independent pathways. Furthermore, we confirmed that these responses are organ- and species-specific for HCFs based on experiments using different types of human and murine fibroblast cell lines. These results suggest potentially new mechanisms of DOX-induced cardiotoxicity from the viewpoint of fibrotic changes in cardiac fibroblasts.
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.