AI Article Synopsis
- The study investigates the role of SOX9 in the healing process after acute kidney injury (AKI) and how it influences whether healing leads to fibrosis or not.
- Researchers found that cells successfully regenerating epithelial tissue turn off SOX9, while those struggling to restore normal structure keep it active, leading to chronic issues such as kidney disease.
- The findings highlight a potential biomarker for assessing the state of kidney repair, indicating that SOX9 activity can predict whether regeneration will occur with or without fibrosis.
Article Abstract
The steps governing healing with or without fibrosis within the same microenvironment are unclear. After acute kidney injury (AKI), injured proximal tubular epithelial cells activate SOX9 for self-restoration. Using a multimodal approach for a head-to-head comparison of injury-induced SOX9 lineages, we identified a dynamic SOX9 switch in repairing epithelia. Lineages that regenerated epithelia silenced SOX9 and healed without fibrosis (SOX9). By contrast, lineages with unrestored apicobasal polarity maintained SOX9 activity in sustained efforts to regenerate, which were identified as a SOX9 Cadherin6 cell state. These reprogrammed cells generated substantial single-cell WNT activity to provoke a fibroproliferative response in adjacent fibroblasts, driving AKI to chronic kidney disease. Transplanted human kidneys displayed similar SOX9/CDH6/WNT2B responses. Thus, we have uncovered a sensor of epithelial repair status, the activity of which determines regeneration with or without fibrosis.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345873 | PMC |
| http://dx.doi.org/10.1126/science.add6371 | DOI Listing |
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