1,25(OH)2D3 ameliorates DSS-induced intestinal ferroptosis through the SIRT3–SOD2–mtROS pathway

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry Pub Date : 2025-06-12 DOI:10.1016/j.jnutbio.2025.109999

Hong-Qian Wang , Ya-Wen Zhu , Zi-Yue Dou , Zhuo Chen , Cheng-Cheng Tong , Xue He , Xiao-Han Ma , Jing Guan , De-Xiang Xu , Xi Chen

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引用次数: 0

Abstract

Ferroptosis has been shown to play a significant role in the pathogenesis of ulcerative colitis (UC). This study investigated the effects of 1,25(OH)₂D₃ supplementation on ferroptosis in dextran sulfate sodium (DSS)-evoked colitis. Intestinal VDR was reduced in UC patients. Accordingly, GPX4 was downregulated and ACSL4 was upregulated in the intestine of UC patients. Animal experiments indicated that vitamin D deficiency exacerbated DSS-induced intestinal ferroptosis in mice. Conversely, pretreatment with 1,25(OH)₂D₃ alleviated DSS-induced ferroptosis in mouse intestine. Similarly, 1,25(OH)₂D₃ supplementation inhibited DSS-induced ferroptosis in HT-29 cells. Furthermore, we found decreased intestinal SIRT3 protein and increased acetylated superoxide dismutase 2 (Ac-SOD2) in UC patients. Pretreatment with 1,25(OH)₂D₃ attenuated DSS-induced downregulation of SIRT3 and acetylation of SOD2 in both mouse intestine and HT-29 cells. Moreover, 1,25(OH)₂D₃ pretreatment inhibited mitochondrial reactive oxygen species (mtROS) in DSS-treated HT-29 cells. Finally, transfection with SIRT3 siRNA antagonized the protective effect of 1,25(OH)₂D₃ on ferroptosis in DSS-treated HT-29 cells. Overall, our results suggest that 1,25(OH)₂D₃ alleviates DSS-induced intestinal ferroptosis via the SIRT3-SOD2-mtROS pathway, further supporting the potential use of 1,25(OH)₂D₃ supplementation in UC treatment.

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1,25(OH)2D3通过SIRT3-SOD2-mtROS途径改善dss诱导的肠铁下垂。

铁下垂已被证明在溃疡性结肠炎（UC）的发病机制中起重要作用。本研究探讨了补充1,25(OH)2D3对葡聚糖硫酸钠（DSS）诱发的结肠炎中铁下垂的影响。UC患者肠道VDR降低。因此，UC患者肠道中GPX4下调，ACSL4上调。动物实验表明，维生素D缺乏加重了dss诱导的小鼠肠道铁下垂。相反，125 (OH)2D3预处理可减轻dss诱导的小鼠肠道铁下垂。同样，补充1,25(OH)2D3可抑制dss诱导的HT-29细胞铁下垂。此外，我们发现UC患者肠道SIRT3蛋白降低，乙酰化超氧化物歧化酶2 （Ac-SOD2）升高。在小鼠肠道和HT-29细胞中，1,25(OH)2D3预处理可减弱dss诱导的SIRT3下调和SOD2乙酰化。此外，1,25(OH)2D3预处理可抑制dss处理HT-29细胞的线粒体活性氧（mtROS）。最后，转染SIRT3 siRNA可拮抗1,25(OH)2D3对dss处理的HT-29细胞铁下垂的保护作用。总之，我们的研究结果表明，125 (OH)2D3通过SIRT3-SOD2-mtROS途径缓解dss诱导的肠道铁下垂，进一步支持补充125 (OH)2D3在UC治疗中的潜在应用。

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

Journal of Nutritional Biochemistry 医学-生化与分子生物学

CiteScore

9.50

自引率

3.60%

发文量

237

审稿时长

68 days

期刊介绍： Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.