Knockdown of KLF11 attenuates hypoxia/reoxygenation injury via JAK2/STAT3 signaling in H9c2.

KLF11 is a Krüppel-like factor (KLF) family member, which plays a central role in cardiac hypertrophy and cerebrovascular protection during ischemic insults. However, the roles of KLF11 in hypoxia/reoxygenation (H/R) injury of rat cardiomyocytes H9c2 have not been elucidated. The aim of this study was to evaluate the effects of KLF11 on H/R injury and investigate the molecular mechanisms involved. Here, we found that KLF11 was increased following H/R and reached the highest level with 24 h hypoxia followed by 12 h reoxygenation. Moreover, we found that inhibition of KLF11 by small RNA suppressed cell apoptosis, the activity of caspase3, the expression of cleaved-caspase3 and cytochrome C in the cytoplasm and the damage of mitochondrial membrane induced by H/R in H9c2, suggesting that KLF11 silencing protects against H/R injury. In addition, we observed that knockdown of KLF11 elevated the expression of p-JAK2 and p-STAT3 in H9c2, and AG490, a selective inhibitor of JAK2/STAT3 abrogated the potential roles of KLF11 in cell apoptosis and mitochondrial damage. In aggregates, our results showed that depletion of KLF11 protected H9c2 against H/R injury through activating the JAK2/STAT3 signaling pathway, suggesting that KLF11 may be provide therapeutic targets for H/R or other heart diseases.