Restoration of NRF2 attenuates myocardial ischemia reperfusion injury through mediating microRNA-29a-3p/CCNT2 axis.
Biofactors
; 47(3): 414-426, 2021 May.
Article
en En
| MEDLINE
| ID: mdl-33600051
ABSTRACT
Accumulated studies have been implemented for comprehending the mechanism of myocardial ischemia reperfusion injury (MI/RI). Nuclear factor erythroid-2 related factor 2 (NRF2)-mediated transcription activity in MI/RI has not been completely interpreted from the perspective of microRNA-29a-3p (miR-29a-3p) and cyclin T2 (CCNT2). Therein, this study intends to decode the mechanism of NRF2/miR-29a-3p/CCNT2 axis in MI/RI. Rat MI/RI models were established by left anterior descending artery ligation. Rats were injected with NRF2 or CCNT2 overexpression plasmids or miR-29a-3p agomir to explore their effects on MI/RI. Hypoxia/reoxygenation (H/R) cardiomyocytes were established and transfected with restored NRF2 or miR-29a-3p or CCNT2 for further exploration of their roles. NRF2, miR-29a-3p, and CCNT2 expression in myocardial tissues in rats with MI/RI and in cardiomyocytes in H/R injury were detected. ChIP assay verified the relationship between miR-29a-3p and NRF2, and the bioinformatics software and dual-luciferase reporter experiment verified the interaction between miR-29a-3p and CCNT2. NRF2 and miR-29a-3p were down-regulated while CCNT2 was up-regulated in myocardial tissues in rats with MI/RI and in H/R-treated cardiomyocytes. Restoration of NRF2 or miR-29a-3p improved hemodynamics and myocardial injury and suppressed serum inflammation and cardiomyocyte apoptosis via CCNT2 in rats with MI/RI. Upregulation of NRF2 or miR-29a-3p inhibited LDH and CK-MB activities, oxidative stress, and apoptosis and promoted viability of cardiomyocytes with H/R injury. NRF2 bound to the promoter of miR-29a-3p and CCNT2 was targeted by miR-29a-3p. This study elucidates that up-regulating NRF2 or miR-29a-3p attenuates MI/RI via inhibiting CCNT2, which may renew the existed knowledge of MI/RI-related mechanism and provide a novel guidance toward MI/RI treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión Miocárdica
/
Isquemia Miocárdica
/
MicroARNs
/
Factor 2 Relacionado con NF-E2
/
Ciclina T
Tipo de estudio:
Etiology_studies
/
Guideline
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biofactors
Asunto de la revista:
BIOQUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China