Pathophysiology of lung injury induced by common bile duct ligation in mice

Fumiaki Shikata, Tomohisa Sakaue, Koh Ichi Nakashiro, Mikio Okazaki, Mie Kurata, Toru Okamura, Masahiro Okura, Masahiro Ryugo, Yuki Nakamura, Takumi Yasugi, Shigeki Higashiyama, Hironori Izutani

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15 Citations (Scopus)

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-a 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.

Original languageEnglish
Article numberA1418
JournalPloS one
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 14 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Shikata, F., Sakaue, T., Nakashiro, K. I., Okazaki, M., Kurata, M., Okamura, T., Okura, M., Ryugo, M., Nakamura, Y., Yasugi, T., Higashiyama, S., & Izutani, H. (2014). Pathophysiology of lung injury induced by common bile duct ligation in mice. PloS one, 9(4), [A1418]. https://doi.org/10.1371/journal.pone.0094550