在糖尿病脏疾病中,二氧酸的积累会导致Podocyte Pyroptosis
Zongwei Zhang1,2, Hongtu Hu1,2, Qiang Luo3
1Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
Journal of cellular and molecular medicine
|December 8, 2023
概括
作为一种葡萄糖代谢产物,二氧酸 (DHAP) 通过激活mTORC1.1.驱动糖尿病病 (DKD) 中的细胞灭. 降低DHAP水平可能为DKD相关的 podocyte损伤提供一种新的治疗策略.
科学领域:
- 代谢途径 代谢途径
- 脏病理生理学脏病理生理学
- 细胞损伤机制 细胞损伤机制
背景情况:
- 糖尿病病 (DKD) 与功能障碍的葡萄糖分解和代谢物积累有关.
- 累积的糖溶性代谢产物,如DHAP在DKD中细胞损伤中的特定作用尚不清楚.
研究的目的:
- 为了研究二氧化酸 (DHAP) 对高葡萄糖诱导的 podocyte pyroptosis 的作用.
- 阐明涉及mTORC1通路的潜在分子机制.
主要方法:
- 代谢和mRNA测序分析db/db小鼠质细胞和高葡萄糖处理的 podocytes.
- 在体外研究中使用siRNA和ALDOB在细胞中的过度表达.
- 评估DHAP水平,mTORC1激活,活性氧物种 (ROS) 和热.
主要成果:
- 在DKD模型中观察到高水平的DHAP和其他糖解代谢物.
- 高葡萄糖诱导的Podocyte Pyroptosis与增加的ALDOB表达和DHAP水平有关.
- siALDOB 转染减少了 DHAP,mTORC1 激活,ROS 和热,而ALDOB 过度表达则产生了相反的效果.
- 通过拉帕素减弱的ROS产量和热的mTORC1抑制.
结论:
- DHAP是一种关键的代谢产物,通过mTORC1通路激活在高葡萄糖刺激的受体细胞中促进热.
- 准DHAP积累是一个潜在的治疗途径,用于治疗DKD中的podocyte损伤.
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