ArticleJournal of advanced research2025
Sonic hedgehog restrains the ubiquitin-dependent degradation of SP1 to inhibit neuronal/glial senescence associated phenotypes in chemotherapy-induced peripheral neuropathy via the TRIM25-CXCL13 axis.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Guanylate-binding protein 2 (GBP2) drives pancreatic cancer cell proliferation by promoting cell cycle progression via the SP1/SKP2/P27 axis.Journal of translational medicine · 2026Article
- TRIM25 Suppresses Hippocampal Neuronal Autophagy under High Glucose via Ubiquitination and Degradation of SIX2.Journal of molecular neuroscience : MN · 2026Article
- Using an integrated omics approach to uncover the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN).Communications medicine · 2026Review
- Discoidin Domain Receptor 1 Promotes Myocardial Fibrosis by Suppressing Specificity Protein 1 Ubiquitination and Degradation in Male Spontaneously Hypertensive Rats.Journal of the American Heart Association · 2026Article
- Anti-aging effect of Hedgehog signaling.Experimental & molecular medicine · 2026Review
- Breaking the Feedback Loop: A Model of Vicious Cycle for CIPN and Acupuncture-Medication Combination.Cancer management and research · 2026Review
- TRIM25-Mediated INSIG1 Ubiquitination Promotes MASH Progression Through Reprogramming Lipid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Reduce electrical overload via threaded Chinese acupuncture in nerve electrical therapy.Bioactive materials · 2025Article
- Mechanistic Perspectives on Radiation-Induced Skin Injury and the Protective Effects of Berberine.Journal of inflammation research · 2025Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
introductionChemotherapy-induced peripheral neuropathy (CIPN) is a common complication that affects an increasing number of cancer survivors. However, the current treatment options for CIPN are limited. Paclitaxel (PTX) is a widely used chemotherapeutic drug that induces senescence in cancer cells. While previous studies have demonstrated that Sonic hedgehog (Shh) can counteract cellular dysfunction during aging, its role in CIPN remains unknown.
objectivesHerein, the aim of this study was to investigate whether Shh activation could inhibits neuronal/glial senescence and alleviates CIPN.
methodsWe treated ND7/23 neuronal cells and RSC96 Schwann cells with two selective Shh activators (purmorphamine [PUR] and smoothened agonist [SAG]) in the presence of PTX. Additionally, we utilized a CIPN mouse model induced by PTX injection. To assess cellular senescence, we performed a senescence-associated β-galactosidase (SA-β-gal) assay, measured reactive oxygen species (ROS) levels, and examined the expression of P16, P21, and γH2AX. To understand the underlying mechanisms, we conducted ubiquitin assays, LC-MS/MS, H&E staining, and assessed protein expression through Western blotting and immunofluorescence staining.
resultsIn vitro, we observed that Shh activation significantly alleviated the senescence-related decline in multiple functions included SA-β-gal activity, expression of P16 and P21, cell viability, and ROS accumulation in DRG sensory neurons and Schwann cells after PTX exposure. Furthermore, our in vivo experiments demonstrated that Shh activation significantly reduced axonal degeneration, demyelination, and improved nerve conduction. Mechanistically, we discovered that PTX reduced the protein level of SP1, which was ubiquitinated by the E3 ligase TRIM25 at the lysine 694 (K694), leading to increased CXCL13 expression, and we found that Shh activation inhibited PTX-induced neuronal/glial senescence and CIPN through the TRIM25-SP1-CXCL13 axis.
conclusionThese findings provide evidence for the role of PTX-induced senescence in DRG sensory neurons and Schwann cells, suggesting that Shh could be a potential therapeutic target for CIPN.
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