缺乏EHHADH可以调节食,加快糖尿病病中的管间损伤
Shuyan Kan1, Qing Hou1, Jinsong Shi1
1National Clinical Research Center for Kidney Disease, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Cell death discovery
|June 15, 2024
概括
过氧体酶EHHADH缺乏会通过破坏过氧体功能和促进损伤,使糖尿病病恶化. 这项研究揭示了EHHADH是糖尿病脏病中食的关键调节者.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 糖尿病病 (DKD) 是2型糖尿病 (T2D) 的一个主要并发症.
- 过氧体L双功能酶 (EHHADH) 在DKD病变发生过程中的作用尚不清楚.
- EHHADH参与过氧体内的脂肪酸β-氧化.
研究的目的:
- 调查EHHADH表达与糖尿病病之间的关联.
- 为了阐明EHHADH影响糖尿病损伤的机制.
- 确定EHHADH在调节食和过氧体恒常的作用.
主要方法:
- 在T2D患者中,EHHADH水平与DKD严重程度的相关性分析.
- 在EHHADH淘汰赛糖尿病小鼠模型中评估管损伤.
- 使用管状上皮细胞 (RTEC) 与EHHADH敲击的体外研究.
- 对食,过氧体损失和反应性氧物种 (ROS) 水平的调查.
- 用自抑制剂 (3-甲基丁,巴菲洛米辛A1) 和ROS抑制剂进行治疗.
主要成果:
- 内源性EHHADH水平与糖尿病病进展和严重程度有很强的相关性.
- 在糖尿病小鼠中,EHHADH淘汰赛加剧了管损伤.
- 在RTEC中,EHHADH的淘汰导致显著的过氧酶体损失,这表明它在食调节中的作用.
- 通过自抑制剂和NBR1恢复食,并与ROS增加有关.
- 在缺乏EHHADH的细胞中抑制ROS阻断了食.
结论:
- 在糖尿病病中,EHHADH缺乏会加速损伤.
- EHHADH作为食的关键调节剂,影响过氧体恒常.
- 通过EHHADH介导的食失调有助于DKD的发病.
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