ANGPTL4与瘦素受体结合,调节子宫外骨形成
Hongling Hu1,2, Sheng Luo3, Pinglin Lai1
1Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China.
概括
莱普受体 (LepR) 有一个新的连接体,血管蛋白类蛋白4 (ANGPTL4). ANGPTL4通过结合介质细胞上的LepR来调节异型骨化 (HO),促进骨的形成.
科学领域:
- 内分泌学 在内分泌学.
- 骨生物学 骨生物学
- 分子生物学分子生物学
背景情况:
- 通过瘦素受体 (LepR) 传递瘦素信号对于代谢调节至关重要.
- 缺乏LepR (db/db) 和缺乏莱普丁 (ob/ob) 的小鼠之间的表型差异表明可能存在额外的LepR配体.
- 莱普R在骨形成等非代谢过程中的作用尚未完全理解.
研究的目的:
- 调查参与超出代谢过程的替代 LepR 配体的潜力.
- 为了确定异型化 (HO) 的新型调节者.
- 阐明LepR信号影响体生成和骨形成的分子机制.
主要方法:
- 在db/db和ob/ob小鼠模型中对切术诱导的异型骨化 (HO) 的比较分析.
- 结体查以确定从棕色脂肪组织中产生的因素.
- 免疫组织化学分析检测在PRRX1+介质细胞上与LepR结合的ANGPTL4.
- 基因操纵包括在特定细胞群体中破坏 LepR 和删除 ANGPTL4.
- 在转基因小鼠中评估体生成和HO形成.
主要成果:
- db/db小鼠,但不是ob/ob小鼠,表现出切术诱导的HO缺陷,表明非勒素依赖的LepR功能.
- 血管蛋白样蛋白4 (ANGPTL4) 被确定为压力和禁食诱导的因素,在切断后释放出来.
- ANGPTL4在HO部位的PRRX1+介质细胞上与LepR结合,促进体生成和HO.
- 在PRRX1+细胞中LepR的遗传破坏,LepR+细胞的切除或ANGPTL4的删除显著损害了原生和HO.
结论:
- 血管蛋白样蛋白4 (ANGPTL4) 被确定为新型瘦素受体 (LepR) 的配体.
- 在PRRX1+介质细胞中,ANGPTL4-LepR信号传递对获得异型化 (HO) 的发展至关重要.
- 这些发现揭示了LepR在调节骨发育和获得的骨形成方面超越了叶黄素信号传递的新角色.
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