title: Prothymosin α overexpression contributes to the development of pulmonary emphysema.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Su
authors.forename: Yau-Lin
authors.initials: YL
authors.lastname: Tseng
authors.forename: Gia-Shing
authors.initials: GS
authors.lastname: Shieh
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Ya-Chieh
authors.initials: YC
authors.lastname: Shiang
authors.forename: Pensee
authors.initials: P
authors.lastname: Wu
authors.forename: Kuo-Jung
authors.initials: KJ
authors.lastname: Li
authors.forename: Te-Hsin
authors.initials: TH
authors.lastname: Yen
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Shiau
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Wu
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011498:Protein Precursors / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D012907:Smoking; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006655:Histone Deacetylases