ArticleJournal of cellular and molecular medicine2019
γ-secretase inhibitor DAPT mitigates cisplatin-induced acute kidney injury by suppressing Notch1 signaling.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Biomarker selection and reporting architecture in human proximal tubularFrontiers in toxicology · 2026Pooled it
- Acute kidney injury: pathogenesis and therapeutic interventions.Molecular biomedicine · 2025Review
- Mechanisms of Acute Kidney Injury-Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities.Biomolecules · 2025Review
- Investigation of the Molecular Mechanism of Asthma in Meishan Pigs Using Multi-Omics Analysis.Animals : an open access journal from MDPI · 2025Article
- Gamma secretase inhibitors, DAPT and MK0752, exhibit synergistic anticancer effects with cisplatin and docetaxel in 2D and 3D models of breast cancer.Turkish journal of biology = Turk biyoloji dergisi · 2025Article
- Lipoxin A4 improves myocardial ischemia/reperfusion injury through the Notch1-Nrf2 signaling pathway.Open life sciences · 2025Article
- A low-dose pemetrexed-cisplatin combination regimen induces significant nephrotoxicity in mice.BMC nephrology · 2024Article
- Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Doxorubicin-Induced Fetal Mesangial Cell Death Occurs Independently of TRPC6 Channel Upregulation but Involves Mitochondrial Generation of Reactive Oxygen Species.International journal of molecular sciences · 2021Article
- Inhibition of fibroblast growth factor-inducible 14 attenuates experimental tubulointerstitial fibrosis and profibrotic factor expression of proximal tubular epithelial cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
- Regulated cell death in cisplatin-induced AKI: relevance ofAmerican journal of physiology. Renal physiology · 2021Article
- Notch inhibitor mitigates renal ischemia‑reperfusion injury in diabetic rats.Molecular medicine reports · 2020Article
- The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity.International journal of molecular sciences · 2019Review
- Inhibition of JAK2/STAT3 signaling pathway protects mice from the DDP-induced acute kidney injury in lung cancer.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Article
- Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury.International journal of molecular sciences · 2019Review
- Pharmacological inhibition of TRPV4 channels protects against ischemia-reperfusion-induced renal insufficiency in neonatal pigs.Clinical science (London, England : 1979) · 2019Article
- Arsenic Trioxide Suppresses Tumor Growth through Antiangiogenesis via Notch Signaling Blockade in Small-Cell Lung Cancer.BioMed research international · 2019Article
- γ-secretase inhibitor DAPT mitigates cisplatin-induced acute kidney injury by suppressing Notch1 signaling.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Organ toxicity, including kidney injury, limits the use of cisplatin for the treatment of multiple human cancers. Hence, interventions to alleviate cisplatin-induced nephropathy are of benefit to cancer patients. Recent studies have demonstrated that pharmacological inhibition of the Notch signaling pathway enhances cisplatin efficacy against several cancer cells. However, whether augmentation of the anti-cancer effect of cisplatin by Notch inhibition comes at the cost of increased kidney injury is unclear. We show here that treatment of mice with cisplatin resulted in a significant increase in Notch ligand Delta-like 1 (Dll1) and Notch1 intracellular domain (N1ICD) protein expression levels in the kidneys. N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor reversed cisplatin-induced increase in renal N1ICD expression and plasma or urinary levels of predictive biomarkers of acute kidney injury (AKI). DAPT also mitigated cisplatin-induced tubular injury and reduction in glomerular filtration rate. Real-time multiphoton microscopy revealed marked necrosis and peritubular vascular dysfunction in the kidneys of cisplatin-treated mice which were abrogated by DAPT. Cisplatin-induced Dll1/Notch1 signaling was recapitulated in a human proximal tubule epithelial cell line (HK-2). siRNA-mediated Dll1 knockdown and DAPT attenuated cisplatin-induced Notch1 cleavage and cytotoxicity in HK-2 cells. These data suggest that Dll1-mediated Notch1 signaling contributes to cisplatin-induced AKI. Hence, the Notch signaling pathway could be a potential therapeutic target to alleviate renal complications associated with cisplatin chemotherapy.
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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.