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MicroRNA-34a promotes iNOS secretion from pulmonary macrophages in septic suckling rats through activating STAT3

Dong-Liang Cheng1, Hong-Xing Fang2, Yuan Liang3

  • 1Department of Pediatric, Henan Provincial People's Hospital, Zhengzhou, 450000, PR China; Department of Pediatric, People's Hospital of Zhengzhou University, Zhengzhou, 450000, PR China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|July 20, 2018
PubMed

Insights

This study reveals microRNA-34a (miR-34a) promotes pediatric sepsis by activating the STAT3 pathway and increasing iNOS production. Inhibiting miR-34a protects against sepsis-induced lung injury, offering a potential therapeutic target.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Immunology

Background:

  • Pediatric sepsis is a leading global cause of mortality, with high death rates despite advanced treatments.
  • Identifying novel therapeutic targets for pediatric sepsis is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of microRNA-34a (miR-34a) in the pathogenesis of pediatric sepsis.
  • To explore the potential of targeting miR-34a for sepsis treatment.

Main Methods:

  • Investigated miR-34a expression in lipopolysaccharide (LPS)-induced macrophages and U937 cells.
  • Assessed the effect of miR-34a inhibition on inducible nitric oxide synthase (iNOS) and STAT3 pathway activation.
  • Utilized cecal ligation and puncture (CLP) models in cell lines, lung tissues, and suckling rats.

Main Results:

  • miR-34a was upregulated in LPS-induced pulmonary macrophages and U937 cells.
  • miR-34a silence decreased iNOS production by inactivating the STAT3 pathway in vitro and in vivo.
  • High miR-34a expression increased iNOS and STAT3 levels, while its inhibition protected against lung injury in a rat model.

Conclusions:

  • miR-34a promotes iNOS secretion in sepsis via the STAT3 pathway, contributing to lung injury.
  • Targeting miR-34a presents a promising therapeutic strategy for pediatric sepsis.

Keywords:
MicroRNA-34aPulmonary macrophagesSTAT3 pathwaysSepsisiNOS

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