Upregulation of microRNA-451 attenuates myocardial I/R injury by suppressing HMGB1

PLoS One. 2020 Jul 17;15(7):e0235614. doi: 10.1371/journal.pone.0235614. eCollection 2020.

Abstract

Both MicroRNAs and HMGB1 took part in pathological process of myocardial I/R injury though several signaling pathways. We hypothesized that mircoRNA451 (miR-451), a group of small non-coding RNAs, could improve this injury by inhibiting HMGB1. Male SD rats were randomly distributed into 5 groups and subjected to I/R process. After 24 hours of reperfusion injury, the serum content of CK and LDH, the content of MDA in tissue and activity of SOD were detected; The infarcted areas were defined by TTC staining and Evans Blue; TUNEL staining and cleaved-Caspase 3 were used to test apoptosis; HMGB1 was detected by real-time fluorescence quantitative PCR and Western Blotting. Compared with the I/R and I/R+Ad-GFP group, upregulation of miR-451 could reduce the infarcted areas, cardiomyocytes apoptosis index, expression of cleaved-caspase 3 and content of CK and LDH significantly(P<0.05); Meanwhile, upregulation of miR-451 could also obviously inhibit HMGB1, the increase of MDA and the decrease of SOD (P<0.05). So this study revealed that upregulation of miR-451 could prevent myocardial I/R injury by suppressing HMGB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • HMGB1 Protein / genetics*
  • HMGB1 Protein / metabolism
  • Male
  • Malondialdehyde / metabolism
  • MicroRNAs / genetics*
  • Myocardial Reperfusion Injury / genetics*
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Up-Regulation*

Substances

  • HMGB1 Protein
  • MIRN451A microRNA, rat
  • MicroRNAs
  • Malondialdehyde
  • Superoxide Dismutase

Grants and funding

This study was partially supported by a grant from National Natural Science foundation of China (No. 81100146, Hu Xiaorong and 81370308, Hu Xiaorong) and a grant from Natural Science foundation of Hubei (No.2015CFB701, Hu Xiaorong) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20110141120060, Hu Xiaorong) and the Fundamental Research Funds of Wuhan City (No.2013070104010044, Hu Xiaorong). The URLs of the funders’ websites are: nsfc.gov.cn, jhsb.hbstd.gov.cn/main/index.jsp, and www.cutech.edu.cn/cn/kyjj/A0103index_1.htm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.