In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 317, No. 2 ( 2019-08-01), p. C253-C261
Kurzfassung:
Myocardial ischemia-reperfusion (I/R) is a common and lethal disease that threatens people’s life worldwide. The underlying mechanisms are under intensive study and yet remain unclear. Here, we explored the function of miR-322/503 in myocardial I/R injury. We used isolated rat perfused heart as an in vivo model and H9c2 cells subjected with the oxygen and glucose deprivation followed by reperfusion as in vitro model to study myocardial I/R injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure the infarct size, and terminal deoxynucleotidyl transferase dUTP-mediated nick-end label (TUNEL) staining was used to examine apoptosis. Quantitative RT-PCR and Western blot were used to determine expression levels of miR-322/503, Smad ubiquitin regulatory factor 2 (Smurf2), enhancer of zeste homolog 2 (EZH2), p-Akt, and p-GSK3β. Overexpression of miR-322/503 decreased infarct size, inhibited cell apoptosis, and promoted cell proliferation through upregualtion of p-Akt and p-GSK3β. Thus the expression of miR-322/503 was reduced during I/R process. On the molecular level, miR-322/503 directly bound Smurf2 mRNA and suppressed its translation. Smurf2 ubiquitinated EZH2 and degraded EZH2, which could activate Akt/GSK3β signaling. Our study demonstrates that miR-322/503 plays a beneficial role in myocardial I/R injury. By inhibition of Smurf2 translation, miR-322/503 induces EZH2 expression and activates Akt/GSK3β pathway, thereby protecting cells from ischemia reperfusion injury.
Materialart:
Online-Ressource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00375.2018
Sprache:
Englisch
Verlag:
American Physiological Society
Publikationsdatum:
2019
ZDB Id:
1477334-X
SSG:
12
