ArticleKidney diseases (Basel, Switzerland)2021
Synergistic Inhibition of Renal Fibrosis by Nintedanib and Gefitinib in a Murine Model of Obstructive Nephropathy.
Article in Kidney diseases (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Nintedanib Attenuates Epidural Fibrosis after Laminectomy in Rats.Journal of Korean Neurosurgical Society · 2026Article
- Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Lyn, a Src kinase family member, is a promising therapeutic target for sepsis-associated acute kidney injury.Annals of translational medicine · 2025Article
- Pathogenic Pathways and Therapeutic Strategies in Autosomal Dominant Polycystic Kidney Disease (ADPKD).Journal of cellular signaling · 2025Article
- Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.Biomolecules & therapeutics · 2024Review
- Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets.Journal of clinical medicine · 2024Review
- Review
- Identification of Fibrotic Biomarkers Associated with Macrophages in Diabetic Nephropathy.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Nintedanib Alleviates Chronic Pancreatitis by Inhibiting the Activation of Pancreatic Stellate Cells via the JAK/STAT3 and ERK1/2 Pathways.Digestive diseases and sciences · 2023Article
- Renal Fibrosis in Lupus Nephritis.International journal of molecular sciences · 2022Review
- Nintedanib induces senolytic effect via STAT3 inhibition.Cell death & disease · 2022Article
- Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury.Biomolecules · 2022Review
- Delayed Administration of Nintedanib Ameliorates Fibrosis Progression in CG-Induced Peritoneal Fibrosis Mouse Model.Kidney diseases (Basel, Switzerland) · 2022Article
- Fatty acid nitroalkene reversal of established lung fibrosis.Redox biology · 2022Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundOur recent studies demonstrated that both nintedanib, an FDA-approved quadruple kinase inhibitor, and gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, protect against obstructive kidney disease. It remains unknown whether they have a synergistic effect.
methodsIn this study, we investigated the effect of combined administration of nintedanib and gefitinib on renal fibrosis in a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO).
resultsCombined treatment with nintedanib and gefitinib after UUO resulted in a greater antifibrotic effect compared with their individual application. Mechanistically, administration of nintedanib blocked UUO-induced phosphorylation of multiple kinase receptors associated renal fibrosis, including platelet-derived growth factor receptors, fibroblast growth factor receptors, vascular endothelial growth factor receptors, and Src family kinase, while gefitinib inhibited EGFR phosphorylation. Their combination also exhibited a more pronounced effect in reducing expression of tissue inhibitors of metalloproteinase-2 (TIMP-2), increasing expression of matrix metalloproteinase-2 (MMP-2), and suppressing renal proinflammatory cytokine expression and macrophage infiltration in the injured kidney. Furthermore, simultaneous administration of nintedanib and gefitinib was more potent in inhibiting UUO-induced renal phosphorylation of signal transducer and activator of transcription-3 (STAT3), nuclear factor-κB, and Smad-3 compared with monotherapy. In cultured renal interstitial fibroblasts, cotreatment with these 2 inhibitors also had synergistic effects in abrogating transforming growth factor β1-induced activation of renal fibroblasts and phosphorylation of Akt, STAT3, and Smad3.
conclusionsCombined application of nintedanib and gefitinib has a synergistic antifibrotic effect in the kidney and may hold translational potential for the treatment of chronic kidney disease.
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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.