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PLoS One. 2015 Jun 8;10(6):e0129590. doi: 10.1371/journal.pone.0129590. eCollection 2015.

Collagenase mRNA Overexpression and Decreased Extracellular Matrix Components Are Early Events in the Pathogenesis of Emphysema.

Author information

1
Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
2
Department of Phatology, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
3
Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil; University City of São Paulo, São Paulo, São Paulo, Brazil.
4
Center for Natural and Human Sciences, UFABC, Santo André, São Paulo, Brazil.

Abstract

To describe the progression of parenchymal remodeling and metalloproteinases gene expression in earlier stages of emphysema, mice received porcine pancreatic elastase (PPE) instillation and Control groups received saline solution. After PPE instillation (1, 3, 6 hours, 3 and 21 days) we measured the mean linear intercept, the volume proportion of types I and III collagen, elastin, fibrillin and the MMP-1, -8, -12 and -13 gene expression. We observed an initial decrease in type I (at the 3rd day) and type III collagen (from the 6th hour until the 3rd day), in posterior time points in which we detected increased gene expression for MMP-8 and -13 in PPE groups. After 21 days, the type III collagen fibers increased and the type I collagen values returned to similar values compared to control groups. The MMP-12 gene expression was increased in earlier times (3 and 6 hours) to which we detected a reduced proportion of elastin (3 days) in PPE groups, reinforcing the already established importance of MMP-12 in the breakdown of ECM. Such findings will be useful to better elucidate the alterations in ECM components and the importance of not only metalloelastase but also collagenases in earlier emphysema stages, providing new clues to novel therapeutic targets.

PMID:
26052708
PMCID:
PMC4460048
DOI:
10.1371/journal.pone.0129590
[Indexed for MEDLINE]
Free PMC Article

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