Multiplexed Human Gene Expression Analysis Reveals a Central Role of the TLR/mTOR/PPARγ and NFkB Axes in Burn and

Cressida Mahung1, Shannon M Wallet2,3, Jordan E Jacobs1

  • 1North Carolina Jaycee Burn Center, Department of Surgery, Chapel Hill, NC 27514, USA.

Insights

Burn and inhalation injuries disrupt immune and metabolic pathways. Identifying key genes like DEPTOR and RPTOR in peripheral blood mononuclear cells (PBMCs) may reveal biomarkers for burn patient outcomes.

Area of Science:

  • Immunology
  • Metabolomics
  • Genomics

Background:

  • Burn patients experience severe immune and metabolic dysfunction.
  • Inhalation injury significantly increases burn patient mortality.
  • Understanding immunometabolic signaling is crucial for managing burn injuries.

Purpose of the Study:

  • To identify specific immune and metabolic signaling pathways in burn (B), inhalation (I), and combined burn-inhalation (BI) injuries.
  • To investigate gene expression in peripheral blood mononuclear cells (PBMCs) of burn patients.
  • To correlate gene expression with clinical outcomes like BMI, length of stay, and mortality.

Main Methods:

  • Utilized nanoString multiplex technology for unbiased gene expression profiling.
  • Analyzed mRNA from PBMCs of 36 injured patients and 12 healthy controls within 72 hours of injury.
  • Employed bioinformatic tools to infer cellular perturbations and signaling pathways from gene expression patterns.

Main Results:

  • mTOR, PPARγ, TLR, and NF-kB signaling pathways were significantly altered in B and BI injuries compared to controls.
  • DEPTOR, LAMTOR5, PPARγ, and RPTOR gene expression correlated with patient BMI.
  • RPTOR correlated with length of stay, and MRC1 correlated with mortality risk.

Conclusions:

  • Specific immunometabolic signaling pathways are dysregulated in burn and inhalation injuries.
  • Certain genes (DEPTOR, LAMTOR5, PPARγ, RPTOR, MRC1) show potential as biomarkers for clinical outcomes.
  • Identifying these mediators could lead to improved therapeutic strategies for burn patients.

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