Details

Autor(en) / Beteiligte

• Su, Bing-Hua
• Tseng, Yau-Lin
• Shieh, Gia-Shing
• Chen, Yi-Cheng
• Shiang, Ya-Chieh
• Wu, Pensee
• Li, Kuo-Jung
• Yen, Te-Hsin
• Shiau, Ai-Li
• Wu, Chao-Liang

Titel

Prothymosin α overexpression contributes to the development of pulmonary emphysema

Ist Teil von

• Nature communications, 2013, Vol.4 (1), p.1906-1906, Article 1906

Ort / Verlag

England: Nature Pub. Group

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.