激活骨质细胞USP26通路通过降低胰岛素抵抗来缓解多器官纤维化
Jiyuan Tang1, Wenkai Ye1, Liang He1
1Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 19, 2025
概括
骨质细胞功能障碍,与胰岛素抵抗 (IR) 相关,导致多器官纤维化. 在骨质母细胞中删除乌比基特异性酶26 (USP26) 会使这种情况恶化,但激活USP26可能会预防纤维化.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 骨质细胞功能障碍与全身代谢障碍和胰岛素抵抗 (IR) 有关.
- 骨质细胞功能障碍,IR和多器官纤维化之间的相互作用形成了一个关键的病理途径.
- 乌比基特异性酶26 (USP26) 在这个轴上的作用尚不清楚.
研究的目的:
- 在IR和多器官纤维化背景下研究USP26在骨质母细胞中的作用.
- 阐明将骨质母细胞功能障碍,USP26和纤维化联系在一起的分子机制.
- 确定潜在的治疗策略,针对骨质母细胞中USP26通路.
主要方法:
- 利用遗传删除模型研究骨质母细胞中USP26的功能.
- 在KSRP促进体区域分析了基因组乳糖化 (H3K18LA).
- 评估基因表达,mRNA替代拼接和FSTL1水平.
- 研究了USP26对IR,血糖,AGE积累和多器官纤维化的影响.
主要成果:
- 骨质母细胞中USP26的删除导致骨形成受损,并诱导与IR相关的多器官纤维化.
- 在KSRP促进体中,USP26的损失降低了H3K18LA,降低了KSRP的表达,并改变了FSTL1mRNA拼接.
- 升高的FSTL1表达与IR相关,高血糖,AGE积累和纤维化.
- 骨质细胞USP26通路的激活显示出预防IR诱导的多器官纤维化的潜力.
结论:
- 骨质细胞USP26在调节骨形成和预防IR相关的多器官纤维化方面发挥着至关重要的作用.
- USP26-KSRP-FSTL1轴是关键的调解器,将骨健康与代谢功能障碍联系起来.
- 向骨质细胞USP26为治疗代谢障碍中的多器官纤维化提供了一个有希望的治疗途径.
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