Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31772-9
Keywords
-
Categories
Funding
- NIH [DK076077, DK087635, DK105821]
- German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [BA 6205/2-1]
Ask authors/readers for more resources
This study reveals the key differences between adaptive and fibrotic repair in the kidney through single-cell analysis, and identifies druggable pathways for pharmacological intervention.
The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic repair are poorly understood. We developed a model of adaptive and fibrotic kidney regeneration by titrating ischemic injury dose. We performed detailed biochemical and histological analysis and profiled transcriptomic changes at bulk and single-cell level (> 110,000 cells) over time. Our analysis highlights kidney proximal tubule cells as key susceptible cells to injury. Adaptive proximal tubule repair correlated with fatty acid oxidation and oxidative phosphorylation. We identify a specific maladaptive/profibrotic proximal tubule cluster after long ischemia, which expresses proinflammatory and profibrotic cytokines and myeloid cell chemotactic factors. Druggability analysis highlights pyroptosis/ferroptosis as vulnerable pathways in these profibrotic cells. Pharmacological targeting of pyroptosis/ferroptosis in vivo pushed cells towards adaptive repair and ameliorates fibrosis. In summary, our single-cell analysis defines key differences in adaptive and fibrotic repair and identifies druggable pathways for pharmacological intervention to prevent kidney fibrosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available