线粒体透性过渡调节剂,环素D,在脂肪生成过程中被C/EBP转录激活
Chen Yu1, Rubens Sautchuk2, John Martinez3
1Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA; Department of Pathology, University of Rochester, Rochester, New York, USA.
The Journal of biological chemistry
|November 10, 2023
概括
老化的骨髓 stromal 细胞 (BMSCs) 转变为脂肪细胞,增加线粒体功能障碍. 脂肪生成激活环素D (CypD),将炎症与老化骨中的改变细胞命运联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 衰老研究研究 衰老研究
背景情况:
- 与年龄相关的骨质损失包括骨形成的减少和脂肪积累的增加.
- 在衰老过程中,介质干细胞的分化转向脂肪生成.
- 线粒体功能障碍,通过MPTP开放,与老年骨质损失有关.
研究的目的:
- 在BMSC脂肪生成过程中调查线粒体功能和环素D (CypD) 调节.
- 在BMSC中确定链接脂肪生成,炎症和线粒体功能障碍的分子机制.
主要方法:
- 对BMSC向脂肪生成的分化进行分析.
- 测量线粒体透性过渡孔 (MPTP) 活动.
- 评估CypD表达及其通过转录因子的调节.
- 对糖解和线粒体网络形态学的研究.
主要成果:
- 在BMSCs中的脂肪生成与增加的CypD表达和MPTP活动有关.
- 葡萄糖分解被激活,线粒体网络在脂肪生成过程中碎片化.
- 原转录因子C/EBPα直接激活了CypD基因 (Ppif) 的表达.
- NF-κB与C/EBPα协同作用,诱导Ppif的表达.
结论:
- 在BMSCs中的脂肪生成涉及改变线粒体功能和形态.
- 在脂肪生成过程中,C/EBPα是CypD的关键转录激活剂.
- 通过C/EBPα和NF-κB对CypD的协同调节表明,在衰老中,脂肪生成,炎症和线粒体功能障碍之间存在联系.
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