Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways
Abstract Excessive exposure to ultraviolet B (UVB) radiation induces oxidative stress and inflammatory responses, accelerating the senescence process of skin cells. Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is typically administered to patients with peripheral T-cell lymphoma, cuta...
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-95624-4 |
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| author | Qianlong Dai Zhiwei Wang Xue Wang Wei Lian Yuchen Ge Shujia Song Fuxing Li Bingxiang Zhao Lihua Li Xiaobo Wang Min Zhou Jianjie Cheng |
| author_facet | Qianlong Dai Zhiwei Wang Xue Wang Wei Lian Yuchen Ge Shujia Song Fuxing Li Bingxiang Zhao Lihua Li Xiaobo Wang Min Zhou Jianjie Cheng |
| author_sort | Qianlong Dai |
| collection | DOAJ |
| description | Abstract Excessive exposure to ultraviolet B (UVB) radiation induces oxidative stress and inflammatory responses, accelerating the senescence process of skin cells. Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is typically administered to patients with peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or multiple myeloma. However, its effect on UVB-induced skin photoaging remains unclear. In this study, we used UVB to induce senescence in human immortalized keratinocyte cell line (HaCaT cells) and skin photoaging in Balb/c mice to investigate the potential of SAHA in mitigating photoaging. First, we established a UVB-induced photoaging model in HaCaT cells. We observed that UVB exposure significantly upregulated the activity of senescence-associated β-galactosidase, p16, p21, IL-1β, IL-6, and matrix metalloproteinases [collagenase (MMP-1), matrix metalloproteinase-3 (MMP-3), and gelatinase (MMP-9)]. Supplementation with SAHA effectively alleviated cellular senescence in HaCaT cells. Next, we used UVB to induce photoaging in Balb/c mouse skin. The study demonstrated that UVB markedly caused skin senescence in Balb/c mice, while SAHA effectively mitigated the changes induced by UVB irradiation. Mechanistically, we found that UVB activated the mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) signaling pathways, whereas SAHA inhibited the upregulation of both mTOR and NF-κB. In summary, these findings suggest that SAHA may protect against UVB-induced cellular senescence and skin photoaging by inhibiting the mTOR and NF-κB signaling pathways. Therefore, SAHA could be a potential anti-senescence agent for mitigating skin photoaging. |
| format | Article |
| id | doaj-art-1d7cbbb5d47446afaa20630a3b74f3c1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1d7cbbb5d47446afaa20630a3b74f3c12025-08-20T03:41:14ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-95624-4Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathwaysQianlong Dai0Zhiwei Wang1Xue Wang2Wei Lian3Yuchen Ge4Shujia Song5Fuxing Li6Bingxiang Zhao7Lihua Li8Xiaobo Wang9Min Zhou10Jianjie Cheng11School of Basic Medicine, Dali UniversitySchool of Basic Medicine, Dali UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Dali UniversitySchool of Basic Medicine, Dali UniversitySchool of Basic Medicine, Dali UniversitySchool of Basic Medicine, Dali UniversitySchool of Basic Medicine, Dali UniversitySchool of Basic Medicine, Dali UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Dali UniversitySchool of Basic Medicine, Dali UniversitySchool of Basic Medicine, Dali UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Dali UniversityAbstract Excessive exposure to ultraviolet B (UVB) radiation induces oxidative stress and inflammatory responses, accelerating the senescence process of skin cells. Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is typically administered to patients with peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or multiple myeloma. However, its effect on UVB-induced skin photoaging remains unclear. In this study, we used UVB to induce senescence in human immortalized keratinocyte cell line (HaCaT cells) and skin photoaging in Balb/c mice to investigate the potential of SAHA in mitigating photoaging. First, we established a UVB-induced photoaging model in HaCaT cells. We observed that UVB exposure significantly upregulated the activity of senescence-associated β-galactosidase, p16, p21, IL-1β, IL-6, and matrix metalloproteinases [collagenase (MMP-1), matrix metalloproteinase-3 (MMP-3), and gelatinase (MMP-9)]. Supplementation with SAHA effectively alleviated cellular senescence in HaCaT cells. Next, we used UVB to induce photoaging in Balb/c mouse skin. The study demonstrated that UVB markedly caused skin senescence in Balb/c mice, while SAHA effectively mitigated the changes induced by UVB irradiation. Mechanistically, we found that UVB activated the mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) signaling pathways, whereas SAHA inhibited the upregulation of both mTOR and NF-κB. In summary, these findings suggest that SAHA may protect against UVB-induced cellular senescence and skin photoaging by inhibiting the mTOR and NF-κB signaling pathways. Therefore, SAHA could be a potential anti-senescence agent for mitigating skin photoaging.https://doi.org/10.1038/s41598-025-95624-4VorinostatUVB-inducedAnti-photoagingmTORNF-κB |
| spellingShingle | Qianlong Dai Zhiwei Wang Xue Wang Wei Lian Yuchen Ge Shujia Song Fuxing Li Bingxiang Zhao Lihua Li Xiaobo Wang Min Zhou Jianjie Cheng Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways Scientific Reports Vorinostat UVB-induced Anti-photoaging mTOR NF-κB |
| title | Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways |
| title_full | Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways |
| title_fullStr | Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways |
| title_full_unstemmed | Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways |
| title_short | Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways |
| title_sort | vorinostat attenuates uvb induced skin senescence by modulating nf κb and mtor signaling pathways |
| topic | Vorinostat UVB-induced Anti-photoaging mTOR NF-κB |
| url | https://doi.org/10.1038/s41598-025-95624-4 |
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