宫内高血糖会诱导SIRT3介导的线粒体功能障碍:早期骨关节炎的胎儿起源病原体
Xinyuan Li1, Wanbo Zhu2, Yi Cheng1
1Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China; Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China; Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
早期的高血糖暴露会增加晚年骨关节炎的风险,因为它会损害线粒体功能和线粒体,与减少Sirt3表达有关. 针对Sirt3的干预措施可以防止骨关节炎的发展.
科学领域:
- 生物医学科学 生物医学科学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 骨关节炎 (OA) 与代谢和炎症状况有关.
- 早期高血糖症对长期OA易受影响的影响尚不清楚.
研究的目的:
- 调查骨关节炎的胎儿起源.
- 探索子宫内高血糖在OA发展中的作用.
- 为OA预防提供有关早期健康保护的见解.
主要方法:
- 在小鼠中诱导的子宫内高血糖症使用链毒素.
- 在后代中使用中介阴茎不稳定性的加速性骨关节炎手术.
- 评估了软骨退化标志物,线粒体功能,以及后代和冠状细胞细胞系中的线粒体衰变.
- 分析了sirt3基因促进剂甲基化水平.
主要成果:
- 宫内高血糖症增加了成年后代的OA易受性.
- 这种敏感性与持续低的Sirt3表达有关.
- 下调的Sirt3 损害了冠状细胞线粒细胞和线粒体功能.
- 过度表达Sirt3或激动剂部分挽救了线粒细胞衰变并缓解了OA的进展.
结论:
- 孕期糖尿病的后代表现出增加的OA敏感性.
- 在子宫内暴露于高血糖会通过表观遗传调节导致OA发作.
- Sirt3在调解早期高血糖症对OA发展的影响方面发挥着至关重要的作用.
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