Bone marrow mesenchymal stem cell-derived exosomes HADH alleviate vitiligo by activating the Nrf2/HO-1 pathway.

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-10-15 DOI:10.1016/j.yexcr.2025.114798

Shiyang Tang, Xin Li, Jianyuan Xi

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引用次数: 0

Abstract

Background: Vitiligo is a chronic skin disorder that significantly impairs patients' quality of life. Exosomes (Exos) have been reported to hold therapeutic promise for vitiligo. This study aimed to investigate the molecular mechanism by which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) ameliorate vitiligo.

Methods: In vitro vitiligo cell model was established by hydrogen peroxide (H₂O₂)-induced melanocytes. A mouse model of vitiligo was also established. Immunofluorescence, cell counting kit-8, 2',7'-dichlorofluorescein diacetate, enzyme linked immunosorbent assay, flow cytometry, real-time quantitative PCR, western blotting, hematoxylin-eosin, Masson-Fontana, and immunohistochemistry staining experiments were elucidated to explore the molecular mechanism of BMSC-Exos in relieving vitiligo.

Results: H₂O₂ treatment reduce the cell viability, superoxide dismutase and catalase activities, and promote reactive oxygen species production, pyroptosis, the expression of NLRP3, ASC, IL-1β and IL-18 proteins in melanocytes. BMSC-Exos treatment effectively counteracted these detrimental effects. Knockdown of exosomal HADH derived from BMSC enhanced H₂O₂-induced oxidative stress and pyroptosis in melanocytes. Mechanistically, BMSC-Exos attenuated H₂O₂-induced oxidative stress and pyroptosis by mediating HADH delivery to activate the Nrf2/HO-1 pathway. Moreover, these results were further confirmed by experiments in a mouse model of vitiligo.

Conclusion: BMSC-Exos can alleviate vitiligo by delivering HADH to activate the Nrf2/HO-1 pathway. This study provides insights for exploring new treatments for vitiligo.

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骨髓间充质干细胞来源的外泌体HADH通过激活Nrf2/HO-1途径缓解白癜风。

背景：白癜风是一种慢性皮肤病，严重影响患者的生活质量。外泌体（Exos）已被报道为白癜风的治疗前景。本研究旨在探讨骨髓间充质干细胞衍生外泌体（BMSC-Exos）改善白癜风的分子机制。方法：采用过氧化氢（H2O2）诱导黑色素细胞建立体外白癜风细胞模型。建立了白癜风小鼠模型。通过免疫荧光、细胞计数试剂盒- 8,2′，7′-二氯荧光素双醋酸酯、酶联免疫吸附、流式细胞术、实时定量PCR、western blotting、苏木精-伊红、Masson-Fontana、免疫组织化学染色等实验，探讨BMSC-Exos缓解白癜风的分子机制。结果：H2O2处理降低了黑素细胞的细胞活力、超氧化物歧化酶和过氧化氢酶活性，促进了活性氧的产生和焦亡，促进了NLRP3、ASC、IL-1β和IL-18蛋白的表达。BMSC-Exos治疗有效地抵消了这些有害影响。BMSC来源的外泌体HADH的敲除增强了h2o2诱导的黑素细胞氧化应激和焦亡。在机制上，BMSC-Exos通过介导HADH传递激活Nrf2/HO-1途径来减弱h2o2诱导的氧化应激和焦亡。此外，这些结果在白癜风小鼠模型的实验中得到进一步证实。结论：BMSC-Exos可通过传递HADH激活Nrf2/HO-1通路缓解白癜风。本研究为探索白癜风的新治疗方法提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.