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

Apoptosis. 2017 Apr;22(4):510-518. doi: 10.1007/s10495-016-1327-1.

Abstract

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.

Keywords: H9c2; Hypoxia/reoxygenation (H/R); JAK2/STAT3; KLF11.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Caspase 3 / physiology
  • Cell Hypoxia
  • Cell Line
  • Culture Media, Serum-Free
  • Janus Kinase 2 / physiology
  • Membrane Potential, Mitochondrial / physiology
  • Myoblasts / metabolism*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology*
  • Myocytes, Cardiac / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Rats
  • STAT3 Transcription Factor / physiology
  • Signal Transduction / physiology*
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Tyrphostins / pharmacology

Substances

  • Culture Media, Serum-Free
  • KLF11 protein, rat
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Trans-Activators
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Jak2 protein, rat
  • Janus Kinase 2
  • Casp3 protein, rat
  • Caspase 3