S100A16 promotes acute kidney injury by activating HRD1-induced ubiquitination and degradation of GSK3ß and CK1α.
Cell Mol Life Sci
; 79(3): 184, 2022 Mar 12.
Article
en En
| MEDLINE
| ID: mdl-35279748
ABSTRACT
The pathogenesis of acute kidney injury (AKI) is associated with the activation of multiple signaling pathways, including Wnt/ß-catenin signaling. However, the mechanism of Wnt/ß-catenin pathway activation in renal interstitial fibroblasts during AKI is unclear. S100 calcium-binding protein A16 (S100A16), a new member of calcium-binding protein S100 family, is a multi-functional signaling factor involved in various pathogenies, including tumors, glycolipid metabolism disorder, and chronic kidney disease (CKD). We investigated the potential participation of S100A16 in Wnt/ß-catenin pathway activation during AKI by subjecting wild-type (WT) and S100A16 knockout (S100A16+/-) mice to the ischemia-reperfusion injury (IRI), and revealed S100A16 upregulation in this model, in which knockout of S100A16 impeded the Wnt/ß-catenin signaling pathway activation and recovered the expression of downstream hepatocyte growth factor (HGF). We also found that S100A16 was highly expressed in Platelet-derived growth factor receptor beta (PDGFRß) positive renal fibroblasts in vivo. Consistently, in rat renal interstitial fibroblasts (NRK-49F cells), both hypoxia/reoxygenation and S100A16 overexpression exacerbated fibroblasts apoptosis and inhibited HGF secretion; whereas S100A16 knockdown or Wnt/ß-catenin pathway inhibitor ICG-001 reversed these changes. Mechanistically, we showed that S100A16 promoted Wnt/ß-catenin signaling activation via the ubiquitylation and degradation of ß-catenin complex members, glycogen synthase kinase 3ß (GSK3ß) and casein kinase 1α (CK1α), mediated by E3 ubiquitin ligase, the HMG-CoA reductase degradation protein 1 (HRD1). Our study identified the S100A16 as a key regulator in the activation of Wnt/ß-catenin signaling pathway in AKI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas S100
/
Ubiquitina-Proteína Ligasas
/
Caseína Quinasa Ialfa
/
Lesión Renal Aguda
/
Glucógeno Sintasa Quinasa 3 beta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Mol Life Sci
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2022
Tipo del documento:
Article
País de afiliación:
China