ArticleProceedings of the National Academy of Sciences of the United States of America2016
Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- Injury-induced electrochemical coupling triggers organ growth.Science advances · 2026Article
- ILP4 and InR regulate paclitaxel-induced hypersensitivity differently inMolecular biology of the cell · 2026Article
- The mucosal-neural axis in chemotherapy-induced gastrointestinal toxicity.Oncology reviews · 2026Review
- A redox-dependent switch governing sensory axon degeneration and regeneration.Scientific reports · 2025Article
- Paclitaxel neurotoxicity is triggered by epidermal EG5-dependent microtubule fasciculation and X-ROS formation.Research square · 2025Article
- Transgenic zebrafish embryos to evaluate the in vivo effects of different liposome-paclitaxel nanocarrier system.Scientific reports · 2025Article
- Alpha-lipoic acid ameliorates nab-paclitaxel-induced peripheral neuropathy by inhibiting IL-17 signaling pathway.Frontiers in immunology · 2025Article
- Single-Cell Analysis of Rohon-Beard Neurons Implicates Fgf Signaling in Axon Maintenance and Cell Survival.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Human apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation.Nature communications · 2024Article
- Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.Frontiers in cellular neuroscience · 2024Article
- Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence.Journal of neurology, neurosurgery, and psychiatry · 2023Review
- Skin Extracellular Matrix Breakdown Following Paclitaxel Therapy in Patients with Chemotherapy-Induced Peripheral Neuropathy.Cancers · 2023Article
- Toxic Effects of Gemcitabine and Paclitaxel Combination: Chemotherapy Drugs Exposure in Zebrafish.Toxics · 2023Article
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- Reversal of Neuralgia Effect of Beta Carotene in Streptozotocin-Associated Diabetic Neuropathic Pain in Female Zebrafish via Matrix Metalloprotease-13 Inhibition.Pharmaceuticals (Basel, Switzerland) · 2023Article
- c-Kit Receptor Maintains Sensory Axon Innervation of the Skin through Src Family Kinases.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Coordinated NADPH oxidase/hydrogen peroxide functions regulate cutaneous sensory axon de- and regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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- Article
- Osteoblasts pattern endothelium and somatosensory axons during zebrafish caudal fin organogenesis.Development (Cambridge, England) · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions.
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Registered trials
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