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

Autor:	Zhou N; Experimental Orthopaedics and Trauma Surgery, Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany., Groven RVM; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.; Division of Trauma Surgery, Department of Surgery, Maastricht University Medical Center+, Maastricht, Netherlands., Horst K; Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany., Mert Ü; Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany., Greven J; Experimental Orthopaedics and Trauma Surgery, Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany., Mollnes TE; Research Laboratory, Nordland Hospital Bodø, Bodø, Norway.; Department of Immunology, Oslo University Hospital, and University of Oslo, Oslo, Norway., Huber-Lang M; Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, Germany., van Griensven M; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands., Hildebrand F; Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany., Balmayor ER; Experimental Orthopaedics and Trauma Surgery, Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Aug 29; Vol. 15, pp. 1402571. Date of Electronic Publication: 2024 Aug 29 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1402571
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Zhou, Groven, Horst, Mert, Greven, Mollnes, Huber-Lang, van Griensven, Hildebrand and Balmayor.)
Databáze:	MEDLINE
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