title: Pathophysiology of lung injury induced by common bile duct ligation in mice.
abstract: BACKGROUND
  Liver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would provide greater insights into the genetic basis of the disease. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches.
  
  
  METHODS
  Eight-week-old Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers was detected by western blot and microarray analyses.
  
  
  RESULTS
  We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down-regulated proteins that were associated with angiogenesis. TNF-α and MMP-9 were highly expressed at 3 weeks after CBDL and were less expressed in the lungs of the control group.
  
  
  CONCLUSIONS
  We constructed a mouse lung injury model by using CBDL. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase. Thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome.
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shikata
authors.affiliation: Department of Cell Growth and Tumor Regulation, Ehime University, Proteo-Science Center, Ehime University, Ehime, Japan; Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Sakaue
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Nakashiro
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Okazaki
authors.affiliation: Department of Pathology, Division of Pathogenomics, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kurata
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okura
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ryugo
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Yasugi
authors.affiliation: Department of Cell Growth and Tumor Regulation, Ehime University, Proteo-Science Center, Ehime University, Ehime, Japan; Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Izutani
mesh_terms: D000818:Animals; D003135:Common Bile Duct / Q000601:surgery*; D004195:Disease Models, Animal; D020065:Hepatopulmonary Syndrome / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008026:Ligation; D008107:Liver Diseases / Q000473:pathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D009504:Neutrophils / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1
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