Prothymosin α overexpression contributes to the development of pulmonary emphysema

Nat Commun. 2013;4:1906. doi: 10.1038/ncomms2906.

Abstract

Emphysema is one of the disease conditions that comprise chronic obstructive pulmonary disease. Prothymosin α transgenic mice exhibit an emphysema phenotype, but the pathophysiological role of prothymosin α in emphysema remains unclear. Here we show that prothymosin α contributes to the pathogenesis of emphysema by increasing acetylation of histones and nuclear factor-kappaB, particularly upon cigarette smoke exposure. We find a positive correlation between prothymosin α levels and the severity of emphysema in prothymosin α transgenic mice and emphysema patients. Prothymosin α overexpression increases susceptibility to cigarette smoke-induced emphysema, and cigarette smoke exposure further enhances prothymosin α expression. We show that prothymosin α inhibits the association of histone deacetylases with histones and nuclear factor-kappaB, and that prothymosin α overexpression increases expression of nuclear factor-kappaB-dependent matrix metalloproteinase 2 and matrix metalloproteinase 9, which are found in the lungs of patients with chronic obstructive pulmonary disease. These results demonstrate the clinical relevance of prothymosin α in regulating acetylation events during the pathogenesis of emphysema.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Line
  • Epithelium / metabolism
  • Epithelium / pathology
  • Histone Deacetylases / metabolism
  • Humans
  • Lung / enzymology
  • Lung / pathology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • NF-kappa B / metabolism
  • Phenotype
  • Protein Precursors / metabolism*
  • Pulmonary Emphysema / enzymology
  • Pulmonary Emphysema / metabolism*
  • Pulmonary Emphysema / pathology*
  • Smoking
  • Thymosin / analogs & derivatives*
  • Thymosin / metabolism
  • Up-Regulation

Substances

  • NF-kappa B
  • Protein Precursors
  • prothymosin alpha
  • Thymosin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Histone Deacetylases