Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury

Brett A. Simon, R. Blaine Easley, Dmitry N. Grigoryev, Shwu Fan Ma, Shui Q. Ye, Tera Lavoie, Rubin M. Tuder, Joe GN Garcia

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Human acute lung injury is characterized by heterogeneous tissue involvement, leading to the potential for extremes of mechanical stress and tissue injury when mechanical ventilation, required to support critically ill patients, is employed. Our goal was to establish whether regional cellular responses to these disparate local mechanical conditions could be determined as a novel approach toward understanding the mechanism of development of ventilator-associated lung injury. We utilized cross-species genomic microarrays in a unilateral model of ventilator-associated lung injury in anesthetized dogs to assess regional cellular responses to local mechanical conditions that potentially contribute pathogenic mechanisms of injury. Highly significant regional differences in gene expression were observed between lung apex/base regions as well as between gravitationally dependent/nondependent regions of the base, with 367 and 1,544 genes differentially regulated between these regions, respectively. Major functional groupings of differentially regulated genes included inflammation and immune responses, cell proliferation, adhesion, signaling, and apoptosis. Expression of genes encoding both acute lung injury-associated inflammatory cytokines and protective acute response genes were markedly different in the nondependent compared with the dependent regions of the lung base. We conclude that there are significant differences in the local responses to stress within the lung, and consequently, insights into the cellular responses that contribute to ventilator-associated lung injury development must be sought in the context of the mechanical heterogeneity that characterizes this syndrome.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number5
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Mechanical Stress
Acute Lung Injury
Lung Injury
Mechanical Ventilators
Microarray Analysis
Lung
Genes
Gene Expression
Wounds and Injuries
Artificial Respiration
Critical Illness
Cell Adhesion
Cell Proliferation
Dogs
Apoptosis
Cytokines
Inflammation

Keywords

  • Adult respiratory distress syndrome
  • Canine
  • Computed tomography
  • Cross-species microarray
  • Mechanical ventilation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury. / Simon, Brett A.; Easley, R. Blaine; Grigoryev, Dmitry N.; Ma, Shwu Fan; Ye, Shui Q.; Lavoie, Tera; Tuder, Rubin M.; Garcia, Joe GN.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 291, No. 5, 2006.

Research output: Contribution to journalArticle

Simon, Brett A. ; Easley, R. Blaine ; Grigoryev, Dmitry N. ; Ma, Shwu Fan ; Ye, Shui Q. ; Lavoie, Tera ; Tuder, Rubin M. ; Garcia, Joe GN. / Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2006 ; Vol. 291, No. 5.
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