Chemokine (C-C motif) Ligand 6 Aggravates Hypoxia Reoxygenation-induced Apoptosis in H9c2 Cells Through Enhancing the Expression of Insulin-like Growth Factor 2-Antisense

J Cardiovasc Pharmacol. 2020 Nov;76(5):549-555. doi: 10.1097/FJC.0000000000000905.


Chemokine (C-C motif) ligand 6 (CCL6), one of the small cytokines in the CC chemokine family, has been reported to involve in renal ischemia-reperfusion (I/R) injury. However, the role of CCL-6 in myocardial I/R injury is nonelucidated. In this study, we used in vitro H9c2 cell model to investigate the overall contributions of CCL6 to myocardial I/R injury. We found the elevated level of CCL6 from the reanalysis of data set GSE-4105 and in hypoxia-reoxygenation (H/R)-injured H9c2 cells. CCL6 silencing attenuated the cardiomyocyte apoptosis induced by H/R injury, whereas exogenous CCL6 treatment aggravated the apoptosis of H/R-injured H9c2 cells. During CCL6 administration, the expression of numerous long noncoding RNAs was differentially regulated. Quantitative RT-Polymerase chain reaction assay demonstrated that insulin-like growth factor 2 (IGF2)-Antisense (AS) had the highest induction by CCL6 addition. IGF2-AS silencing alleviated the apoptosis of H/R-injured H9c2 cells. Collectively, we have identified a potential mechanism by which high expression of CCL6 contributes to the H/R-induced apoptosis in H9c2 cells through enhancing the expression of IGF2-AS. These findings also give evidence of the feasibility of CCL6 or long noncoding RNA IGF2-AS as a potential target for modulation or therapeutic intervention in myocardial I/R injury.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Hypoxia
  • Cell Line
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism*
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / pathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Rats
  • Signal Transduction


  • Ccl6 protein, rat
  • Chemokines, CC
  • Igf2 protein, rat
  • RNA, Long Noncoding
  • Insulin-Like Growth Factor II