title: Knockdown of KLF11 attenuates hypoxia/reoxygenation injury via JAK2/STAT3 signaling in H9c2.
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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China. boyucad@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000502:physiology; D015687:Cell Hypoxia; D002460:Cell Line; D016895:Culture Media, Serum-Free; D053614:Janus Kinase 2 / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; C569356:KLF11 protein, rat; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: H9c2; Hypoxia/reoxygenation (H/R); JAK2/STAT3; KLF11