Pulmonary miRNA expression after polytrauma depends on the surgical invasiveness and displays an anti-inflammatory pattern by the combined inhibition of C5 and CD14

Front Immunol. 2024 Aug 29:15:1402571. doi: 10.3389/fimmu.2024.1402571. eCollection 2024.

Abstract

Background: Respiratory failure can be a severe complication after polytrauma. Extensive systemic inflammation due to surgical interventions, as well as exacerbated post-traumatic immune responses influence the occurrence and progression of respiratory failure. This study investigated the effect of different surgical treatment modalities as well as combined inhibition of the complement component C5 and the toll-like receptor molecule CD14 (C5/CD14 inhibition) on the pulmonary microRNA (miRNA) signature after polytrauma, using a translational porcine polytrauma model.

Methods: After induction of general anesthesia, animals were subjected to polytrauma, consisting of blunt chest trauma, bilateral femur fractures, hemorrhagic shock, and liver laceration. One sham group (n=6) and three treatment groups were defined; Early Total Care (ETC, n=8), Damage Control Orthopedics (DCO, n=8), and ETC + C5/CD14 inhibition (n=4). Animals were medically and operatively stabilized, and treated in an ICU setting for 72 h. Lung tissue was sampled, miRNAs were isolated, transcribed, and pooled for qPCR array analyses, followed by validation in the individual animal population. Lastly, mRNA target prediction was performed followed by functional enrichment analyses.

Results: The miRNA arrays identified six significantly deregulated miRNAs in lung tissue. In the DCO group, miR-129, miR-192, miR-194, miR-382, and miR-503 were significantly upregulated compared to the ETC group. The miRNA expression profiles in the ETC + C5/CD14 inhibition group approximated those of the DCO group. Bioinformatic analysis revealed mRNA targets and signaling pathways related to alveolar edema, pulmonary fibrosis, inflammation response, and leukocytes recruitment. Collectively, the DCO group, as well as the ETC + C5/CD14 inhibition group, revealed more anti-inflammatory and regenerative miRNA expression profiles.

Conclusion: This study showed that reduced surgical invasiveness and combining ETC with C5/CD14 inhibition can contribute to the reduction of pulmonary complications.

Keywords: ARDS; damage control orthopedics; early total care; microRNAs; polytrauma; respiratory failure.

MeSH terms

  • Animals
  • Complement C5* / antagonists & inhibitors
  • Complement C5* / genetics
  • Complement C5* / metabolism
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lipopolysaccharide Receptors* / genetics
  • Lipopolysaccharide Receptors* / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • MicroRNAs* / genetics
  • Multiple Trauma* / genetics
  • Multiple Trauma* / immunology
  • Swine

Substances

  • MicroRNAs
  • Lipopolysaccharide Receptors
  • Complement C5

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft), project number 429837092 to MH-L and FH, and by the Province of Limburg, Limburg Invests in its Knowledge Economy (LINK) to MG. The author NZ is financially funded by the China Scholarship Council (CSC) under Grant 202106160019.