期刊论文详细信息
eLife
Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair
Lori L O'Brien1  Yoshihiko Kobayashi2  Aleksandra Tata2  Purushothama Rao Tata3  Shintaro Ide4  Steven D Crowley4  Savannah Herbek4  Koki Abe4  Sarah A Strausser4  Kana Ide4  Laura Barisoni5  Tomokazu Souma6 
[1] Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, United States;Department of Cell Biology, Duke University School of Medicine, Durham, United States;Department of Cell Biology, Duke University School of Medicine, Durham, United States;Regeneration Next, Duke University, Durham, United States;Duke Cancer Institute, Duke University School of Medicine, Durham, United States;Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States;Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States;Department of Pathology, Duke University School of Medicine, Durham, United States;Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States;Regeneration Next, Duke University, Durham, United States;
关键词: single-cell RNA sequencing;    ferroptosis;    kidney injury;    repair;    Mouse;   
DOI  :  10.7554/eLife.68603
来源: eLife Sciences Publications, Ltd
PDF
【 摘 要 】

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.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO202107302846510ZK.pdf 18178KB PDF download
  文献评价指标  
  下载次数:4次 浏览次数:4次