SHP-1 inhibits renal ischemia reperfusion injury via dephosphorylating ASK1 and suppressing apoptosis.
Biochem Biophys Res Commun
; 513(2): 360-367, 2019 05 28.
Article
en En
| MEDLINE
| ID: mdl-30961932
Apoptosis of tubular epithelium cells (TECs) plays critical roles in renal ischemia reperfusion (I/R) injury, but the molecular regulatory mechanisms of apoptosis still require further investigation. Recently, phosphatase family members have been suggested to regulate multiple aspects of the injury and regeneration response. However, the roles of SHP-1, an important protein-tyrosine phosphatase, in the regulation of renal I/R injury remain unknown. Here, we found that SHP-1 knockdown in vivo significantly increased renal I/R injury and aggravated the apoptosis of TECs. Consistently, after SHP-1 knockdown in TECs in vitro, a sharp increase of apoptosis induced by cobalt dichloride was found. The protective role of SHP-1 was also validated in a TEC cell line stably overexpressing SHP-1. Mechanistically, the ASK1/MKK4/JNK pro-apoptosis signal was over activated after SHP-1 knockdown, and SHP-1 could bind to and dephosphorylate ASK1 to inhibit its activation, thus repressing apoptosis.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
/
MAP Quinasa Quinasa Quinasa 5
/
Insuficiencia Renal
/
Proteína Tirosina Fosfatasa no Receptora Tipo 6
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2019
Tipo del documento:
Article