ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Cardiac organoids in toxicology: from construction strategies and research trends to precision screening applications.Stem cell research & therapy · 2026Review
- Inhibiting L-type calcium channel promotes cardiomyocyte proliferation through activating the canonical Wnt signaling pathway.Acta pharmacologica Sinica · 2026Article
- The role and mechanism of NRG1/ErbB4 in inducing the differentiation of induced pluripotent stem cells into cardiomyocytes.BMC cardiovascular disorders · 2024Article
- Advancements in understanding cardiotoxicity of EGFR- TKIs in non-small cell lung cancer treatment and beyond.Frontiers in pharmacology · 2024Review
- Involvement of kallikrein-PAR2-proinflammatory pathway in severe trastuzumab-induced cardiotoxicity.Cancer science · 2022Article
- Review
- Modeling Precision Cardio-Oncology: Using Human-Induced Pluripotent Stem Cells for Risk Stratification and Prevention.Current oncology reports · 2021Review
- Improving cardiotoxicity prediction in cancer treatment: integration of conventional circulating biomarkers and novel exploratory tools.Archives of toxicology · 2021Review
- The Role of Epidermal Growth Factor Receptor Family of Receptor Tyrosine Kinases in Mediating Diabetes-Induced Cardiovascular Complications.Frontiers in pharmacology · 2021Review
- Building Multi-Dimensional Induced Pluripotent Stem Cells-Based Model Platforms to Assess Cardiotoxicity in Cancer Therapies.Frontiers in pharmacology · 2021Review
- Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity.Current cardiology reports · 2020Review
- Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients.Cellular and molecular life sciences : CMLS · 2020Review
- Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity.BMC cardiovascular disorders · 2020Article
- Human Pluripotent Stem Cell-Derived Cardiomyocytes for Assessment of Anticancer Drug-Induced Cardiotoxicity.Frontiers in cardiovascular medicine · 2020Review
- Concise Review: Precision Matchmaking: Induced Pluripotent Stem Cells Meet Cardio-Oncology.Stem cells translational medicine · 2019Review
- Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell.Cardiovascular research · 2019Review
- hiPSCs in cardio-oncology: deciphering the genomics.Cardiovascular research · 2019Review
- Aconitine-induced cardiac arrhythmia in human induced pluripotent stem cell-derived cardiomyocytes.Experimental and therapeutic medicine · 2018Article
- Review
- Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro.International journal of molecular sciences · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ∼570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1β (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy.
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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.