在高葡萄糖诱导的足细胞功能变化中,ADAM17-Klotho交叉的参与
Dorota Rogacka1, Patrycja Rachubik1, Marlena Typiak2
1Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 80-308 Gdansk, Poland.
International journal of molecular sciences
|January 25, 2025
概括
高葡萄糖通过增加ADAM17活性来损害脏细胞,从而降低保护性Klotho水平. 恢复Klotho或抑制ADAM17可以防止糖尿病病的进展.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 糖尿病学 糖尿病学
- 分子生物学分子生物学
背景情况:
- 糖尿病病 (DKD) 的特点是微蛋白尿,与高葡萄糖 (HG) 的 podocyte 损伤和氧化应激有关.
- 在HG条件下,对于podocyte健康至关重要的Klotho蛋白减少.
- ADAM17 (一种分解蛋白和金属蛋白酶17) 调解了Klotho从细胞膜中脱落.
研究的目的:
- 为了研究ADAM17在HG诱导的Klotho在人体皮细胞中的下降中的作用.
- 为了阐明连接HG,ADAM17,Klotho和podocyte功能障碍的机制.
主要方法:
- 培养的人类 podocytes 暴露在高葡萄糖条件下.
- 测量了ADAM17蛋白水平,细胞外活性和NADPH氧化酶活性.
- 评估了质白蛋白的透性和Klotho的表达.
- 使用ADAM17抑制剂和基因沉默技术.
- 用Klotho来评估保护作用.
主要成果:
- HG显著增加了细胞中的ADAM17蛋白和细胞外活性,与增加的白蛋白透性相关.
- 由HG诱导的 podocyte 功能障碍,氧化应激和白蛋白尿症通过ADAM17 抑制或Klotho 补充而逆转.
- 克洛托表达的下调导致细胞外ADAM17活性升高.
结论:
- 过高血糖症通过ADAM17激活加剧 podocyte 功能障碍,导致Klotho 脱落.
- 克洛托通过一个依赖ADAM17的机制在高血糖症中保护细胞功能.
- 针对ADAM17-Klotho轴为糖尿病病提供了一个潜在的治疗策略.
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