期刊
ELIFE
卷 10, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.68603
关键词
-
类别
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK123097, P30 DK114857]
- American Society of Nephrology
- American Heart Association [20POST35210465]
- Astellas Foundation for Research on Metabolic Disorders
- Japan Society for the Promotion of Science
The study reveals that proximal tubular cells develop a pro-inflammatory state following injury, which can lead to persistent inflammation and fibrosis. After mild injury, these inflammatory PT cells transiently appear and make the cells vulnerable to ferroptotic stress; while after severe injury, they accumulate and enhance inflammation and fibrosis.
Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, we show that proximal tubular (PT) cells develop a molecularly distinct, pro-inflammatory state following injury. While these inflammatory PT cells transiently appear after mild injury and return to their original state without inducing fibrosis, after severe injury they accumulate and contribute to persistent inflammation. This transient inflammatory PT state significantly downregulates glutathione metabolism genes, making the cells vulnerable to ferroptotic stress. Genetic induction of high ferroptotic stress in these cells after mild injury leads to the accumulation of the inflammatory PT cells, enhancing inflammation and fibrosis. Our study broadens the roles of ferroptotic stress from being a trigger of regulated cell death to include the promotion and accumulation of proinflammatory cells that underlie maladaptive repair.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据