Signal regulatory protein α protects podocytes through promoting autophagic activity.
JCI Insight
; 52019 03 19.
Article
en En
| MEDLINE
| ID: mdl-30888336
ABSTRACT
High autophagic activity in podocytes, terminally differentiated cells which serve as main components of the kidney filtration barrier, is essential for podocyte survival under various challenges. How podocytes maintain such a high level of autophagy, however, remains unclear. Here we report that signal regulatory protein α (SIRPα) plays a key role in promoting podocyte autophagy. Unlike other glomerular cells, podocytes strongly express SIRPα, which is, however, downregulated in patients with focal segmental glomerulosclerosis and mice with experimental nephropathy. Podocyte SIRPα levels are inversely correlated with the severity of podocyte injury and proteinuria but positively with autophagy. Compared to wild-type littermates, Sirpa-deficient mice display greater age-related podocyte injury and proteinuria and develop more rapid and severe renal injury in various models of experimental nephropathy. Mechanistically, podocyte SIRPα strongly reduces Akt/GSK-3ß/ß-catenin signaling, leading to an increase in autophagic activity. Our findings thus demonstrate a critical protective role of SIRPα in podocyte survival via maintaining autophagic activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteinuria
/
Autofagia
/
Glomeruloesclerosis Focal y Segmentaria
/
Receptores Inmunológicos
/
Antígenos de Diferenciación
/
Podocitos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
JCI Insight
Año:
2019
Tipo del documento:
Article
País de afiliación:
China