Integrating microRNAs into a system biology approach to acute lung injury

Research output: Contribution to journalReview article

67 Scopus citations

Abstract

Acute lung injury (ALI), including the ventilator-induced lung injury (VILI) and the more severe acute respiratory distress syndrome (ARDS), are common and complex inflammatory lung diseases potentially affected by various genetic and nongenetic factors. Using the candidate gene approach, genetic variants associated with immune response and inflammatory pathways have been identified and implicated in ALI. Because gene expression is an intermediate phenotype that resides between the DNA sequence variation and the higher level cellular or whole-body phenotypes, the illustration of gene expression regulatory networks potentially could enhance understanding of disease susceptibility and the development of inflammatory lung syndromes. MicroRNAs (miRNAs) have emerged as a novel class of gene regulators that play critical roles in complex diseases including ALI. Comparisons of global miRNA profiles in animal models of ALI and VILI identified several miRNAs (eg, miR-146a and miR-155) previously implicated in immune response and inflammatory pathways. Therefore, via regulation of target genes in these biological processes and pathways, miRNAs potentially contribute to the development of ALI. Although this line of inquiry exists at a nascent stage, miRNAs have the potential to be critical components of a comprehensive model for inflammatory lung disease built by a systems biology approach that integrates genetic, genomic, proteomic, epigenetic as well as environmental stimuli information. Given their particularly recognized role in regulation of immune and inflammatory responses, miRNAs also serve as novel therapeutic targets and biomarkers for ALI/ARDS or VILI, thus facilitating the realization of personalized medicine for individuals with acute inflammatory lung disease.

Original languageEnglish (US)
Pages (from-to)180-190
Number of pages11
JournalTranslational Research
Volume157
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • ACE
  • ALI
  • ARDS
  • CNV
  • HTV
  • IL
  • LCL
  • LPS
  • PAI-1
  • PBEF
  • SNP
  • SOD3
  • TGF-β
  • THBS1
  • TLR
  • VEGF
  • VILI
  • acute lung injury
  • acute respiratory distress syndrome
  • angiotensin converting enzyme
  • copy number variant
  • extracellular superoxide dismutase
  • high tidal ventilation
  • interleukin
  • lipopolysaccharide
  • lymphoblastoid cell line sample
  • miRNA
  • microRNA
  • plasminogen activator inhibitor 1
  • pre-B-cell colony enhancing factor
  • single nucleotide polymorphism
  • thrombospondin 1
  • toll-like receptor
  • transforming growth factor β
  • vascular endothelial growth factor
  • ventilator-induced lung injury

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical
  • Physiology (medical)

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