减少雌激素信号传递有助于骨质损失和心脏功能障碍,在interleukin-10淘汰赛小鼠中
Sanmi E Alake1, John Ice1, Kara Robinson1
1Department of Nutritional Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
Physiological reports
|January 12, 2024
概括
在小鼠中,互白素-10缺乏会导致肠道炎症,骨质损失和心脏问题. 雌激素减少和骨矿化受损导致FGF23增加,导致心脏纤维化.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 心血管生物学 心血管生物学
- 骨生物学 骨生物学 骨生物学
背景情况:
- 介质蛋白-10 (IL-10) 对于免疫调节至关重要.
- IL-10淘汰赛 (KO) 的小鼠表现出慢性肠道炎症,心血管功能障碍和骨质损失.
- IL-10在肠道,骨和心血管系统之间的器官间通信中的作用尚未完全理解.
研究的目的:
- 研究IL-10在肠道,骨和心血管系统之间的交叉对话中的作用.
- 为了描述IL-10 KO小鼠的生理变化.
- 阐明将IL-10缺乏与多器官功能障碍联系在一起的机制.
主要方法:
- 在3个月或6个月内比较IL-10KO小鼠和野生类型 (WT) 对应物.
- 对炎症标记物,Fgf23和与骨相关的基因 (Dmp1,Phex) 的基因表达的评估.
- 测量血清17β-雌激醇 (E2) 和心脏蛋白质表达 (pNOS3).
- 评估肠道细菌β-葡萄糖酶活性和卵巢Cyp19a1mRNA水平.
- 在试验室中用E2.2治疗阴道淋巴细胞.
主要成果:
- IL-10KO小鼠的IL17a和TnfmRNA增加,骨和心脏Il6mRNA增加.
- 骨Dmp1和PhexmRNA在IL-10KO小鼠中被抑制,导致Fgf23mRNA和纤维化增加了约4倍.
- 肠道细菌β-葡萄糖酶活性和卵巢Cyp19a1mRNA在IL-10KO小鼠中较低,与降低的血清E2和心脏PNOS3相关.
- 在WT小鼠中,E2治疗减少了肠道炎症,但不能减少IL-10KO小鼠的炎症.
结论:
- 在IL-10 KO小鼠中,雌激素水平降低和骨矿化受损有助于增加FGF23.
- 在没有IL-10的情况下,高FGF23会加剧心脏纤维化.
- 在肠-骨-心血管轴内,IL-10在维持器官间通信和恒温中起着至关重要的作用.
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