Abstract:
BACKGROUND:The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination of in vivo and ex vivo models together with ECM remodeling markers may provide a translational tool for screening of potential treatments for IPF. METHODS:Twenty female Sprague-Dawley rats, twelve weeks of age, were administrated either two doses of bleomycin (BLM) (n = 14) or saline (n = 6) I.T., two days apart. Ten rats were euthanized at day seven and the remaining ten rats at day fourteen, after the last dose. Precision-cut lung slices (PCLS) were made and cultured for 48 h. Ten female Sprague-Dawley rats, twelve weeks of age, were administrated either two doses of BLM (n = 7) or saline (n = 3) I.T., two days apart. The rats were euthanized fourteen days after the last dose. PCLS were made and cultured for 48 h in: medium, medium + 100 μM IBMX (PDE inhibitor), or medium + 10 μM GM6001 (MMP inhibitor). Turnover of type I collagen (P1NP, C1M), type III collagen (iP3NP, C3M) and elastin degradation (ELM7) was measured in the supernatant of the cultured PCLS. RESULTS:P1NP, C1M, iP3NP, C3M and ELM7 were significantly increased in supernatants from BLM animals (P ≤ 0.05 - P ≤ 0.0001) when compared to controls. P1NP, C1M, iP3NP, C3M and ELM7 were significantly increased in supernatants from day seven BLM animals compared to day fourteen BLM animals (P ≤ 0.05 - P ≤ 0.0001). P1NP, C1M, iP3NP, C3M and ELM7 were significantly decreased when adding IBMX to the culture medium of fibrotic lung tissue (P ≤ 0.05 - P ≤ 0.0001). C1M, C3M and ELM7 were significantly decreased when adding GM6001 to the culture medium (P ≤ 0.05 - P ≤ 0.0001). Sirius Red and Orcein staining confirmed the presence of collagen and elastin deposition in the lungs of the animals receiving BLM. CONCLUSIONS:The protein fingerprint technology allows the assessment of ECM remodeling markers in the BLM PCLS model. By combining in vivo, ex vivo models and the protein fingerprint technology in the fibrotic phase of the model, we believe the chance of translation from animal model to human is markedly increased.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Hansen NU,Karsdal MA,Brockbank S,Cruwys S,Rønnow S,Leeming DJdoi
10.1186/s12931-016-0394-8subject
Has Abstractpub_date
2016-07-05 00:00:00pages
76issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-016-0394-8journal_volume
17pub_type
杂志文章abstract::Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of ...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-016-0391-y
更新日期:2016-06-21 00:00:00
abstract:RATIONALE:Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to efficiently measure β-adrenergic sweat rate and specifically quantify CFTR function in the se...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-25
更新日期:2014-02-25 00:00:00
abstract:BACKGROUND:For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for ...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/1465-9921-8-30
更新日期:2007-04-04 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12931-020-01495-w
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journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/s12931-015-0209-3
更新日期:2015-04-18 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-1318-1
更新日期:2020-02-18 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-58
更新日期:2008-08-05 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-56
更新日期:2012-07-04 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12931-017-0523-z
更新日期:2017-02-21 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12931-015-0172-z
更新日期:2015-02-07 00:00:00
abstract:: ...
journal_title:Respiratory research
pub_type:
doi:10.1186/s12931-018-0930-9
更新日期:2018-12-20 00:00:00
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journal_title:Respiratory research
pub_type: 社论
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更新日期:2014-04-11 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0089-y
更新日期:2014-08-06 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2011-12-21 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12931-015-0265-8
更新日期:2015-09-16 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0551-8
更新日期:2017-04-20 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01361-9
更新日期:2020-04-23 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12931-018-0950-5
更新日期:2018-12-07 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-64
更新日期:2006-04-10 00:00:00
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pub_type: 杂志文章
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更新日期:2020-10-29 00:00:00
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pub_type: 临床试验,杂志文章,多中心研究
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pub_type: 杂志文章,评审
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更新日期:2020-08-17 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:
更新日期:2003-01-01 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-019-1108-9
更新日期:2019-07-08 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01372-6
更新日期:2020-05-27 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,meta分析
doi:10.1186/s12931-020-1309-2
更新日期:2020-02-06 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,多中心研究
doi:10.1186/s12931-017-0686-7
更新日期:2017-12-06 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/1465-9921-6-78
更新日期:2005-07-21 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-42
更新日期:2006-03-22 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0963-0
更新日期:2019-01-03 00:00:00