Researchers from USC and Caltech used advanced technology to map changes in cells, molecules, and structures after acute kidney injury (AKI). Their study, published in Nature Communications, reveals how damaged cells interact in ways that might cause chronic kidney disease (CKD), affecting over 37 million U.S. adults.
These insights could help prevent CKD and kidney failure. The research, supported by a USC Broad Innovation Award, involved teams from Andy McMahon’s lab at USC and Long Cai’s lab at Caltech.
In the study, co-authors Michal Polonsky from Caltech and Louisa Gerhardt from USC used a new tool called seqFISH, developed by Long Cai’s lab, to analyze kidney tissue from mice with acute kidney injury (AKI).
This tool helped them study gene activity and cellular interactions in detail, identify injury-related microenvironments, and predict how AKI might progress to chronic kidney disease (CKD).
Dr. McMahon highlighted that this technology offers new insights into kidney injury, crucial for preventing CKD. At the same time, Dr. Cai emphasized the value of cross-institutional collaborations in advancing research.
Scientists found a harmful area in the kidney’s outer layer called “ME-5,” where damaged proximal tubule cells (PTs) interact with nearby fibroblast cells. These interactions involve genes Clcf1 and Crfl1, which can cause inflammation and scarring. The signals in ME-5 may also attract immune cells, worsening inflammation and fibrosis.
The scientists found another critical area in the kidney, called “ME-16,” with clusters of immune cells known as tertiary lymphoid structures. These structures are linked to long-term inflammation. Unlike ME-5, ME-16 is spread throughout the injured kidney.
The study found that after acute kidney injury (AKI) in mice, cells form harmful interactions that could worsen the condition. These findings highlight how damaged cells contribute to ongoing kidney problems and suggest new targets for treatment.
Journal reference :
- Polonsky, M., Gerhardt, L.M.S., Yun, J. et al. Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease. Nature Communications. DOI:10.1038/s41467-024-51186-z.
