Deletion of the cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis.

BACKGROUND

Sepsis is associated with a high mortality rate. A major cause of death in sepsis patients is respiratory failure, which is characterized by oxidative injury, epithelial apoptosis, and increased lung permeability. MicroRNAs (miRs) are important regulators of sepsis progression.

METHODS

This study aimed to explore the role of in sepsis in mice. Experimental sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP).

RESULTS

CLP significantly induced systemic inflammation, lung permeability, and lung epithelial apoptosis with downregulated messenger RNA (mRNA) levels of antioxidant enzymes. The knockout mice had a lower 48-hour survival rate, higher plasma tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels, and greater pulmonary permeability compared with wild-type mice after CLP. CLP also markedly increased interstitial hemorrhage, collapsed more alveolar sacs, and increased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive and Bcl-2-associated X (Bax)-positive cells in knockout lung tissues, with elevated mRNA levels of and reduced activities of catalase (Cat), glutathione peroxidase 1(Gpx1). negatively regulated 14-3-3ζ expression evidenced in knockout lungs and the A549 cell line. In lipopolysaccharide (LPS)-induced A549 cells, overexpression remarkably suppressed the production of reactive oxygen species, inhibited cell apoptosis, and enhanced levels of protein and related enzymes.

CONCLUSIONS

Deletion of the cluster aggravated sepsis-induced oxidative injury of lung epithelial cells.