Sirt1可能通过Wnt/β-Catenin信号通路减轻HT-2毒素诱导的软骨细胞损伤

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon Pub Date : 2025-06-19 DOI:10.1016/j.toxicon.2025.108465

Haonan Li, Qi Zhang, Fang Qi, Qian Yu, Chenxi Wang, Ying Liu, Haoyu DU, Yue Zhao, Jun Yu

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引用次数: 0

摘要

Sirt1对软骨稳态至关重要，其失调与大骨节病（KBD）有关，这是一种与HT-2毒素暴露有关的骨关节病。本研究探讨Sirt1在HT-2毒素诱导的软骨细胞损伤中的作用。HT-2毒素（0、5、10、20ng/mL）处理48小时后，人胎儿软骨细胞表现出剂量依赖性活力降低、细胞外基质（ECM）降解（↓Collagen II，↓TIMP1，↑MMP13）和衰老（↑P21，↑β-半乳糖苷酶）。HT-2毒素抑制Sirt1，同时激活Wnt/β-catenin信号传导（↑WNT3A，↑β-catenin）。Sirt1激动剂白藜芦醇（25μM）可恢复TIMP1和Collagen II水平，降低P21水平，而不影响MMP13，同时抑制WNT3A/β-catenin通路。这些结果表明Sirt1激活通过抑制Wnt/β-catenin信号传导减轻HT-2毒素诱导的软骨细胞损伤。

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Sirt1 Mitigates HT-2 Toxin-Induced Chondrocyte Injury Potentially via the Wnt/β-Catenin Signaling Pathway.

Sirt1 is crucial for cartilage homeostasis, and its dysregulation is implicated in Kashin-Beck disease (KBD), an osteochondropathy linked to HT-2 toxin exposure. This study investigated Sirt1's role in HT-2 toxin-induced chondrocyte injury. Human fetal chondrocytes treated with HT-2 toxin (0, 5, 10, 20ng/mL) for 48 hours showed dose-dependent viability reduction, extracellular matrix (ECM) degradation (↓Collagen II, ↓TIMP1, ↑MMP13), and senescence (↑P21, ↑β-galactosidase). HT-2 toxin suppressed Sirt1 while activating Wnt/β-catenin signaling (↑WNT3A, ↑β-catenin). Resveratrol (25μM), a Sirt1 agonist, restored TIMP1 and Collagen II levels and reduced P21 without affecting MMP13, while inhibiting the WNT3A/β-catenin pathway. These results demonstrate that Sirt1 activation mitigates HT-2 toxin-induced chondrocyte damage by inhibiting Wnt/β-catenin signaling.

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来源期刊

Toxicon 医学-毒理学

CiteScore

4.80

自引率

10.70%

发文量

358

审稿时长

68 days

期刊介绍： Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee. Toxicon''s "aims and scope" are to publish: -articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms -papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins -molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins -clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained. -material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems. -articles on the translational application of toxins, for example as drugs and insecticides -epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged. -articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon. -review articles on problems related to toxinology. To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.