SOX9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys.
Science
; 383(6685): eadd6371, 2024 Feb 23.
Article
en En
| MEDLINE
| ID: mdl-38386758
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 (SOX9on-off). By contrast, lineages with unrestored apicobasal polarity maintained SOX9 activity in sustained efforts to regenerate, which were identified as a SOX9on-on Cadherin6pos 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Insuficiencia Renal Crónica
/
Factor de Transcripción SOX9
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Lesión Renal Aguda
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Riñón
/
Túbulos Renales Proximales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos