Expression profiling suggests loss of surface integrity and failure of regenerative repair as major driving forces for chronic obstructive pulmonary disease progression

Eslam Samaha, Klemens Vierlinger, Wolfgang Weinhappel, Jasminka Godnic-Cvar, Christa Nöhammer, Dirk Koczan, Hans Juergen Thiesen, Hagai Yanai, Vadim E. Fraifeld, Rolf Ziesche

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Chronic obstructive pulmonary disease (COPD) poses a major risk for public health, yet remarkably little is known about its detailed pathophysiology. Definition of COPD as nonreversible pulmonary obstruction revealing more about spatial orientation than about mechanisms of pathology may be a major reason for this. We conducted a controlled observational study allowing for simultaneous assessment of clinical and biological development in COPD. Sixteen healthy control subjects and 104 subjects with chronic bronchitis, with or without pulmonary obstruction at baseline, were investigated. Using both the extent of and change in bronchial obstruction as main scoring criteria for the analysis of gene expression in lung tissue, we identified 410 genes significantly associated with progression of COPD. One hundred ten of these genes demonstrated a distinctive expression pattern, with their functional annotations indicating participation in the regulation of cellular coherence, membrane integrity, growth, and differentiation, as well as inflammation and fibroproliferative repair. The regulatory pattern indicates a sequentially unfolding pathology that centers on a two-step failure of surface integrity commencing with a loss of epithelial coherence as early as chronic bronchitis. Decline of regenerative repair starting in Global Initiative for Chronic Obstructive Lung Disease stage I then activates degradation of extracellular-matrix hyaluronan, causing structural failure of the bronchial wall that is only resolved by scar formation. Although they require independent confirmation, our findings provide the first tangible pathophysiological concept of COPD to be further explored.

Original languageEnglish
Pages (from-to)441-452
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume64
Issue number4
DOIs
StatePublished - 1 Apr 2021

Keywords

  • COPD mechanisms
  • COPD pathology
  • Regenerative repair
  • Surface integrity

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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