在糖尿病病中,CCDC92缺乏改善了葡萄细胞脂毒性
Fuwen Zuo1, Youzhao Wang1, Xinlei Xu1
1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China.
Metabolism: clinical and experimental
|November 12, 2023
概括
在糖尿病病 (DKD) 中,CCDC92蛋白水平增加,通过破坏脂质平衡来促进细胞损伤. 针对CCDC92可能为DKD患者提供新的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 代谢疾病 代谢疾病
- 分子生物学分子生物学
背景情况:
- 糖尿病病 (DKD) 的特点是细胞损伤,这是一个关键的早期事件.
- 脂质和脂质调节蛋白质在细胞功能和病中起着关键作用.
- 参与脂质新陈代谢和糖尿病的蛋白质CCDC92在病中没有明确的作用.
研究的目的:
- 为了研究CCDC92在中的表达模式.
- 阐明CCDC92在糖尿病病 (DKD) 病原发生中的作用.
- 探索CCDC92对DKD中的Podocyte脂毒性的贡献.
主要方法:
- 在人类脏活检中对CCDC92表达和脂质积累的分析,跨越DKD严重程度.
- 产生特定于 podocyte 的 Ccdc92 淘汰小鼠模型 (db/db 和 HFD/STZ).
- 在这些模型中评估细胞损伤和脂质沉积.
主要成果:
- 在DKD患者的脏活检中,CCDC92水平升高,与降低的eGFR和质脂质积累相关.
- 在糖尿病小鼠模型的脏中诱导了CCDC92的表达,特别是在细胞中.
- 足细胞特异性Ccdc92缺失减弱了糖尿病患者的足细胞损伤和宫外脂质沉积.
- 发现CCDC92促进了细胞脂毒性,部分是通过ABCA1信号传递和脂质稳定性破坏.
结论:
- CCDC92是一种新型的脂质稳定性调节剂,可加剧DKD中的 podocyte损伤.
- 在DKD中,CCDC92可能作为受体细胞损伤的潜在生物标志物.
- 向CCDC92为DKD管理提供了一个有前途的,创新的治疗策略.
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