title: Relationship between expression of matrix metalloproteinase-9 and adenylyl cyclase-associated protein 1 in chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  To investigate the relationship between expression of matrix metalloproteinase (MMP)-9 and expression of adenylyl cyclase-associated protein (CAP)-1 in chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Patients with possible respiratory disease were recruited into the study and divided into a COPD group and a non-COPD group on diagnosis. Pulmonary function tests were performed and serum concentrations of MMP-9 were measured using an enzyme-linked immunosorbent assay. MMP-9 and CAP1 expression were analysed in lung tissue and bronchoalveolar lavage fluid in all available samples using immunohistochemistry and Western blot, respectively. In addition, expression of MMP-9 and CAP1 in vitro was investigated using immunofluorescence. Expression of CAP1 in response to MMP-9 was measured in the human alveolar epithelial cell line HP-AEpiC, using Western blot.
  
  
  RESULTS
  A total of 90 patients were included in the study: 52 were in the COPD group and 38 in the non-COPD group. Serum MMP-9 concentrations were significantly higher in the COPD than in the non-COPD group. MMP-9 serum concentrations were negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1 as a percentage of the normal predicted value and the ratio of FEV1 to forced vital capacity, and were positively correlated with residual volume (RV), total lung capacity (TLC) and RV/TLC values. In lung tissue and bronchoalveolar lavage fluid samples, MMP-9 and CAP1 expression were inversely related. This relationship was confirmed in HP-AEpiC cells. High expression of MMP-9 and low expression of CAP1 was demonstrated in the COPD group compared with the non-COPD group.
  
  
  CONCLUSIONS
  This study demonstrated an inverse relationship between CAP1 and MMP-9 expression, and high expression of MMP-9 and low expression of CAP1 in those with COPD compared with the non-COPD group. Overexpression of MMP-9 in lung tissue and its interaction with CAP1 is likely to play a major role in airway obstruction in COPD.
authors.affiliation: Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Shuan-Shuan
authors.initials: SS
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China Department of Respiratory Medicine, St Luke's Hospital, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Respiratory Medicine, St Luke's Hospital, Shanghai, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Duan
authors.affiliation: Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China wang-chang-hui@hotmail.com.
authors.forename: Chang-Hui
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis* / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000378:metabolism; D014109:Total Lung Capacity / Q000502:physiology
chemical_list: C489549:CAP1 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000262:Adenylyl Cyclases
keywords: Matrix metalloproteinase-9; adenylyl cyclase-associated protein 1; chronic obstructive pulmonary disease