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在糖尿病病中,MAPK1通过PACS-2-依赖机制调解MAM干扰和线粒体功能障碍

Shanshan Liu^1,2,3,4, Shuai Han^1,2,3,4, Cuili Wang^1,2,3,4

¹Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

International journal of biological sciences

|January 3, 2024

概括

糖尿病病涉及线粒体问题. 向MAPK1-PACS-2通路可以通过恢复线粒体相关的内分泌网膜膜连接来防止损伤.

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
细胞生物学细胞生物学
生物化学生物化学

背景情况:

糖尿病病 (DKD) 是末期病 (ESRD) 的主要原因.
管中的线粒体功能障碍是DKD病变的早期事件,但分子机制尚未完全理解.
与线粒体关联的细胞内网膜 (MAM) 在细胞健康中起着至关重要的作用,并与各种疾病有关.

研究的目的:

为了研究线粒体相关的内细胞网膜 (MAM) 在糖尿病病 (DKD) 中的作用.
在DKD中确定将高葡萄糖与线粒体功能障碍联系起来的分子途径.
探索DKD的潜在治疗点.

主要方法:

在高葡萄糖条件下检查了糖尿病人和小鼠脏,以及人类脏HK-2细胞.
评估了MAM完整性,线粒体形态和MAPK1和PACS-2等关键蛋白质的表达的变化.
利用细胞培养实验来操纵PACS-2水平,以及在糖尿病小鼠中涉及MAPK1抑制的体内研究.

主要成果:

高葡萄糖会破坏MAM,并在细胞和组织中引起线粒体碎片化.
高葡萄糖增加了基因激活蛋白激酶1 (MAPK1) 的活性,从而降低了酸酸分类蛋白2 (PACS-2) 的水平.
在实验模型中,恢复PACS-2水平或抑制MAPK1保护MAM干扰和线粒体分裂.

结论:

MAPK1-PACS-2信号轴是DKD病变发生的关键途径.
由高葡萄糖引起的MAM中断,由MAPK1-诱导的PACS-2的减少介导,有助于DKD中的线粒体功能障碍.
针对MAPK1-PACS-2通路代表了DKD的一个有前途的治疗策略.

关键词:

在MAPK1中,它是MAPK1.在 PACS-2 系统中,我们可以使用 PACS-2.糖尿病病糖尿病病线粒体中的线粒体.线粒体关联的内塑性网膜膜膜.

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