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Functional Characterization of a Porcine Emphysema Model

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Abstract

Background

Lung emphysema is a central feature of chronic obstructive pulmonary disease (COPD), a frequent human disease worldwide. Cigarette smoking is the major cause of COPD, but genetic predisposition seems to be an important factor. Mutations in surfactant protein genes have been linked to COPD phenotypes in humans. Also, the catalytic activities of metalloproteinases (MMPs) are central in the pathogenesis of emphysema/COPD. Especially MMP9, but also MMP2, MMP7, and MMP12 seem to be involved in human emphysema. MMP12−/− mice are protected from smoke-induced emphysema. ITGB6−/− mice spontaneously develop age-related lung emphysema due to lack of ITGB6-TGF-β1 regulation of the MMP12 expression.

Methods

A mutated pig phenotype characterized by age-related lung emphysema and resembling the ITGB6−/− mouse has been described previously. To investigate the emphysema pathogenesis in this pig model, we examined the expression of MMP2, MMP7, MMP9, MMP12, and TGF-β1 by quantitative PCR (qPCR). In addition, immunohistochemical stainings of the lungs with SP-B, SP-C, MMP9, and MMP12 antibodies were performed. The haematologic/immunologic status of the pigs also was studied.

Results

The qPCR study showed no difference between pigs with and without emphysema, and no systemic differences were indicated by the haematologic and immunologic studies. However, the immunohistochemical stainings showed an increased expression of MMP9 and MMP12 in older, mutated pigs (with emphysema) compared with normal and young mutated pigs (without emphysema).

Conclusions

The pig model is comparable to human emphysema patients and the ITGB6−/− mouse model with respect to both morphology and functionality.

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Acknowledgments

Special thanks to Thomas Mark for assistance with the qPCR statistics.

Conflict of interest

None

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Authors and Affiliations

  1. Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark

    Camilla Sichlau Bruun, Susanna Cirera, Claus Bøttcher Jørgensen & Merete Fredholm

  2. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark

    Louise Kruse Jensen, Páll Skuli Leifsson & Henrik Elvang Jensen

  3. National Veterinary Institute, Technical University of Denmark, Lindholm, 4771, Kalvehave, Denmark

    Jens Nielsen

Authors
  1. Camilla Sichlau Bruun
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  2. Louise Kruse Jensen
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  3. Páll Skuli Leifsson
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  4. Jens Nielsen
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  5. Susanna Cirera
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  6. Claus Bøttcher Jørgensen
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  7. Henrik Elvang Jensen
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  8. Merete Fredholm
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Corresponding author

Correspondence to Camilla Sichlau Bruun.

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Bruun, C.S., Jensen, L.K., Leifsson, P.S. et al. Functional Characterization of a Porcine Emphysema Model. Lung 191, 669–675 (2013). https://doi.org/10.1007/s00408-013-9504-2

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  • DOI: https://doi.org/10.1007/s00408-013-9504-2

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