Adipose Gene Expression Profile Changes With Lung Allograft Reperfusion

Am J Transplant. 2017 Jan;17(1):239-245. doi: 10.1111/ajt.13964. Epub 2016 Aug 18.

Abstract

Obesity is a risk factor for primary graft dysfunction (PGD), a form of lung injury resulting from ischemia-reperfusion after lung transplantation, but the impact of ischemia-reperfusion on adipose tissue is unknown. We evaluated differential gene expression in thoracic visceral adipose tissue (VAT) before and after lung reperfusion. Total RNA was isolated from thoracic VAT sampled from six subjects enrolled in the Lung Transplant Body Composition study before and after allograft reperfusion and quantified using the Human Gene 2.0 ST array. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment for genes involved in complement and coagulation cascades and Jak-STAT signaling pathways. Overall, 72 genes were upregulated and 56 genes were downregulated in the postreperfusion time compared with baseline. Long pentraxin-3, a gene and plasma protein previously associated with PGD, was the most upregulated gene (19.5-fold increase, p = 0.04). Fibronectin leucine-rich transmembrane protein-3, a gene associated with cell adhesion and receptor signaling, was the most downregulated gene (4.3-fold decrease, p = 0.04). Ischemia-reperfusion has a demonstrable impact on gene expression in visceral adipose tissue in our pilot study of nonobese, non-PGD lung transplant recipients. Future evaluation will focus on differential adipose tissue gene expression and the development of PGD after transplant.

Keywords: genomics; ischemia reperfusion injury (IRI); lung (allograft) function/dysfunction; lung transplantation/pulmonology; translational research/science.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Adult
  • Aged
  • Allografts
  • Biomarkers / metabolism
  • C-Reactive Protein / genetics*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Transplantation / adverse effects*
  • Male
  • Membrane Proteins / genetics*
  • Obesity / physiopathology*
  • Pilot Projects
  • Primary Graft Dysfunction / etiology*
  • Primary Graft Dysfunction / pathology
  • Prognosis
  • Prospective Studies
  • Reperfusion
  • Risk Factors
  • Serum Amyloid P-Component / genetics*
  • Transcriptome*

Substances

  • Biomarkers
  • FLRT3 protein, human
  • Membrane Proteins
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein