| First Author | Su BH | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 1906 | PubMed ID | 23695700 |
| Mgi Jnum | J:270215 | Mgi Id | MGI:6209860 |
| Doi | 10.1038/ncomms2906 | Citation | Su BH, et al. (2013) Prothymosin alpha overexpression contributes to the development of pulmonary emphysema. Nat Commun 4:1906 |
| abstractText | Emphysema is one of the disease conditions that comprise chronic obstructive pulmonary disease. Prothymosin alpha transgenic mice exhibit an emphysema phenotype, but the pathophysiological role of prothymosin alpha in emphysema remains unclear. Here we show that prothymosin alpha 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 alpha levels and the severity of emphysema in prothymosin alpha transgenic mice and emphysema patients. Prothymosin alpha overexpression increases susceptibility to cigarette smoke-induced emphysema, and cigarette smoke exposure further enhances prothymosin alpha expression. We show that prothymosin alpha inhibits the association of histone deacetylases with histones and nuclear factor-kappaB, and that prothymosin alpha 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 alpha in regulating acetylation events during the pathogenesis of emphysema. |
