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

Fabíola S Z Robertoni,Chin J Lin,Ana Paula P Velosa,Fernanda Degobbi T Q S Lopes,Milton A Martins,Beatriz M Saraiva-Romanholo,Juliana D Lourenço,Sérgio D Sasaki,Cláudia M Fló,Clarice R Olivo,Natália G Gonçalves,Walcy R Teodoro,Carlos E Ambrósio

doi:10.1371/journal.pone.0129590

Fabíola S Z Robertoni, Chin J Lin + Show 11 more

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https://doi.org/10.1371/journal.pone.0129590

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Journal: PloS one	Publication Date: Jun 8, 2015
Citations: 13	License type: CC BY 4.0

Affiliation: Universidade de São Paulo, Universidade Federal do ABC

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.

Highlights

The imbalance between proteinases and anti-proteinases is still accepted as the primary mediator of parenchymal destruction in emphysema [1,2,3,4,5] and is attested by studies in which the matrix metalloproteinases (MMPs) have demonstrated an important role in attacking the protein components of the lung parenchyma extracellular matrix (ECM) [6,7].PLOS ONE | DOI:10.1371/journal.pone.0129590 June 8, 2015Collagenase mRNA Overexpression in Earlier Stages of Emphysema
We evaluated the gene expression for metalloelastase and for collagenases MMP-1, -8 and to better understand the role of collagenases in emphysema development and progression, which remain understudied
Our analysis revealed an initial decrease in ECM fibers amount, which had occurred at times later than when we detected increases in polimorphonuclear leukocytes in parenchyma and in gene expression for collagenases MMP-8, -13 and for metalloelastase-12; only 21 days following emphysema induction we detected increases in some of the ECM fiber amounts in porcine pancreatic elastase (PPE) groups

Summary

Introduction

The imbalance between proteinases and anti-proteinases is still accepted as the primary mediator of parenchymal destruction in emphysema [1,2,3,4,5] and is attested by studies in which the matrix metalloproteinases (MMPs) have demonstrated an important role in attacking the protein components of the lung parenchyma extracellular matrix (ECM) [6,7].PLOS ONE | DOI:10.1371/journal.pone.0129590 June 8, 2015Collagenase mRNA Overexpression in Earlier Stages of Emphysema. The imbalance between proteinases and anti-proteinases is still accepted as the primary mediator of parenchymal destruction in emphysema [1,2,3,4,5] and is attested by studies in which the matrix metalloproteinases (MMPs) have demonstrated an important role in attacking the protein components of the lung parenchyma extracellular matrix (ECM) [6,7]. Collagenase mRNA Overexpression in Earlier Stages of Emphysema

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