Cargando…

Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice

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 d...

Descripción completa

Detalles Bibliográficos
Autores principales: Shikata, Fumiaki, Sakaue, Tomohisa, Nakashiro, Koh-ichi, Okazaki, Mikio, Kurata, Mie, Okamura, Toru, Okura, Masahiro, Ryugo, Masahiro, Nakamura, Yuki, Yasugi, Takumi, Higashiyama, Shigeki, Izutani, Hironori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986091/
https://www.ncbi.nlm.nih.gov/pubmed/24733017
http://dx.doi.org/10.1371/journal.pone.0094550
_version_ 1782311665822334976
author Shikata, Fumiaki
Sakaue, Tomohisa
Nakashiro, Koh-ichi
Okazaki, Mikio
Kurata, Mie
Okamura, Toru
Okura, Masahiro
Ryugo, Masahiro
Nakamura, Yuki
Yasugi, Takumi
Higashiyama, Shigeki
Izutani, Hironori
author_facet Shikata, Fumiaki
Sakaue, Tomohisa
Nakashiro, Koh-ichi
Okazaki, Mikio
Kurata, Mie
Okamura, Toru
Okura, Masahiro
Ryugo, Masahiro
Nakamura, Yuki
Yasugi, Takumi
Higashiyama, Shigeki
Izutani, Hironori
author_sort Shikata, Fumiaki
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3986091
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-39860912014-04-15 Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice Shikata, Fumiaki Sakaue, Tomohisa Nakashiro, Koh-ichi Okazaki, Mikio Kurata, Mie Okamura, Toru Okura, Masahiro Ryugo, Masahiro Nakamura, Yuki Yasugi, Takumi Higashiyama, Shigeki Izutani, Hironori PLoS One Research Article 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. Public Library of Science 2014-04-14 /pmc/articles/PMC3986091/ /pubmed/24733017 http://dx.doi.org/10.1371/journal.pone.0094550 Text en © 2014 Shikata et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shikata, Fumiaki
Sakaue, Tomohisa
Nakashiro, Koh-ichi
Okazaki, Mikio
Kurata, Mie
Okamura, Toru
Okura, Masahiro
Ryugo, Masahiro
Nakamura, Yuki
Yasugi, Takumi
Higashiyama, Shigeki
Izutani, Hironori
Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice
title Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice
title_full Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice
title_fullStr Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice
title_full_unstemmed Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice
title_short Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice
title_sort pathophysiology of lung injury induced by common bile duct ligation in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986091/
https://www.ncbi.nlm.nih.gov/pubmed/24733017
http://dx.doi.org/10.1371/journal.pone.0094550
work_keys_str_mv AT shikatafumiaki pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT sakauetomohisa pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT nakashirokohichi pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT okazakimikio pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT kuratamie pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT okamuratoru pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT okuramasahiro pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT ryugomasahiro pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT nakamurayuki pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT yasugitakumi pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT higashiyamashigeki pathophysiologyoflunginjuryinducedbycommonbileductligationinmice
AT izutanihironori pathophysiologyoflunginjuryinducedbycommonbileductligationinmice