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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen Type I / metabolism
  • Collagen Type III / metabolism
  • Collagenases / genetics*
  • Collagenases / metabolism
  • Elastin / metabolism
  • Extracellular Matrix / metabolism*
  • Immunohistochemistry
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice, Inbred C57BL
  • Neutrophils / metabolism
  • Pulmonary Emphysema / enzymology*
  • Pulmonary Emphysema / genetics*
  • RNA, Messenger / metabolism
  • Sus scrofa

Substances

  • Collagen Type I
  • Collagen Type III
  • RNA, Messenger
  • Elastin
  • Collagenases
  • Matrix Metalloproteinases

Grants and funding

This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant Numbers: 2011/08584-6 and 2012/02957-8); Laboratório de Investigação Médica (LIM 20). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.