RGD Reference Report - Matrix metalloproteinase-9 deficiency worsens lung injury in a model of bronchopulmonary dysplasia. - Rat Genome Database

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Matrix metalloproteinase-9 deficiency worsens lung injury in a model of bronchopulmonary dysplasia.

Authors: Lukkarinen, H  Hogmalm, A  Lappalainen, U  Bry, K 
Citation: Lukkarinen H, etal., Am J Respir Cell Mol Biol. 2009 Jul;41(1):59-68. Epub 2008 Dec 18.
RGD ID: 5129685
Pubmed: PMID:19097983   (View Abstract at PubMed)
DOI: DOI:10.1165/rcmb.2008-0179OC   (Journal Full-text)

Increased activity of matrix metalloproteinase (MMP)-9 is associated with the development of bronchopulmonary dysplasia (BPD) in newborn infants, but the role of MMP-9 in the pathophysiology of BPD is unclear. We have shown that perinatal expression of interleukin-1 beta (IL-1 beta) in the lung is sufficient to cause a BPD-like illness in infant mice. To study the hypothesis that MMP-9 is an important downstream mediator in IL-1 beta-induced lung injury in the newborn, we compared the effects of IL-1 beta on fetal and postnatal lung inflammation and development in transgenic mice with regulatable pulmonary overexpression of human mature IL-1 beta with wild-type (IL-1 beta/MMP-9(+/+)) or null (IL-1 beta/MMP-9(-/-)) MMP-9 loci. IL-1 beta increased the expression of MMP-9 mRNA and amount of MMP-9 protein in the lungs of MMP-9(+/+) mice. IL-1 beta/MMP-9(-/-) mice had fewer neutrophils but more macrophages in the lungs than did IL-1 beta/MMP-9(+/+) mice. MMP-9 deficiency increased pulmonary cell death and macrophage clearance of dying cells in IL-1 beta-expressing mice. IL-1 beta/MMP-9(-/-) mice had more severe alveolar hypoplasia than IL-1 beta/MMP-9(+/+) mice, implying that IL-1 beta-induced lung disease was worsened in the absence of MMP-9. These results suggest that MMP-9 activity in the inflamed neonatal lung protects the lung against injury.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP9Humanbronchopulmonary dysplasia  ISOMmp9 (Mus musculus) RGD 
Mmp9Ratbronchopulmonary dysplasia  ISOMmp9 (Mus musculus) RGD 
Mmp9Mousebronchopulmonary dysplasia  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information