title: Collagenase mRNA Overexpression and Decreased Extracellular Matrix Components Are Early Events in the Pathogenesis of Emphysema.
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.
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Fabíola S Z
authors.initials: FS
authors.lastname: Robertoni
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Clarice R
authors.initials: CR
authors.lastname: Olivo
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Juliana D
authors.initials: JD
authors.lastname: Lourenço
authors.affiliation: Department of Phatology, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Natália G
authors.initials: NG
authors.lastname: Gonçalves
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Ana Paula P
authors.initials: AP
authors.lastname: Velosa
authors.affiliation: Department of Phatology, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Chin J
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Fló
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil; University City of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Saraiva-Romanholo
authors.affiliation: Center for Natural and Human Sciences, UFABC, Santo André, São Paulo, Brazil.
authors.forename: Sérgio D
authors.initials: SD
authors.lastname: Sasaki
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Milton A
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Walcy R
authors.initials: WR
authors.lastname: Teodoro
authors.affiliation: Department of Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Fernanda Degobbi T Q S
authors.initials: FD
authors.lastname: Lopes
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D017364:Collagenases / Q000235:genetics* / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000201:enzymology* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D004549:Elastin; D017364:Collagenases; D020782:Matrix Metalloproteinases