rhTNFR:Fc increases Nrf2 expression via miR-27a mediation to protect myocardium against sepsis injury

Biochem Biophys Res Commun. 2015 Aug 28;464(3):855-61. doi: 10.1016/j.bbrc.2015.07.051. Epub 2015 Jul 11.

Abstract

Objective: Sepsis is a whole-body inflammation disease and can result in septic shock and multiple organ failure. The previous study demonstrated that miR-27a plays a critical role in inflammation regulation. Here, we investigated that effect and its possible mechanism of rhTNFR:Fc on sepsis treatment.

Methods: LPS induced sepsis mice model was established. 10 mg/kg rhTNFR:Fc was used to treat sepsis mice by intravenous injection.

Results: RhTNFR:Fc improved cardiac function of sepsis mice, and markedly decreased miR-27a but increased Nrf2 expression level of myocardium in LPS treated mice. In H9C2 cells, rhTNFR:Fc also increased Nrf2 expression, elevated cell viability and decreased cell apoptosis. However, the effects were reversed by miR-27a mimic. In addition, miR-27a mimic reduced the activity of Nrf2 3'UTR while miR-27a inhibitor elevated enhanced its level.

Conclusion: rhTNFR:Fc activated Nrf2 pathway to protect myocardium against LPS-induced sepsis injury via miR-27a regulation.

Keywords: Nrf2; Sepsis; miR-27a; rhTNFR:Fc.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cardiotonic Agents / pharmacology*
  • Cells, Cultured
  • Etanercept
  • Gene Expression Regulation / drug effects
  • Heart / drug effects*
  • Heart / physiopathology
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / pharmacology*
  • Lipopolysaccharides / toxicity
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myoblasts, Cardiac / drug effects
  • Myoblasts, Cardiac / pathology
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Rats
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • Sepsis / drug therapy*
  • Sepsis / genetics
  • Sepsis / physiopathology

Substances

  • 3' Untranslated Regions
  • Cardiotonic Agents
  • Immunoglobulin G
  • Lipopolysaccharides
  • MIRN27 microRNA, human
  • MIRN27 microRNA, rat
  • MicroRNAs
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Nfe2l2 protein, rat
  • Receptors, Tumor Necrosis Factor
  • Etanercept