Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia: Pathogenetic implications Academic Article uri icon

Overview

MeSH Major

  • Collagenases
  • Gelatinases
  • Hyperoxia
  • Lung
  • Metalloendopeptidases

abstract

  • Subacute hyperoxia may cause basement membrane disruption and subsequent fibrosis. To test the role of extracellular matrix degradation in hyperoxic damage, we analyzed the expression of gelatinases A and B and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 in rats exposed to 85% O2. Oxygen-exposed rats were studied at 1, 3, 5, and 7 days, and compared with air-breathing rats. Lung mRNAs assayed by Northern and in situ hybridization showed an up-regulation of lung gelatinases A and B from the 3rd day on. Gelatinase A was localized in alveolar macrophages and in interstitial and alveolar epithelial cells. Gelatinase B mRNA and protein were localized in macrophages and bronchiolar and alveolar epithelial cells. Increased gelatinase A and B activities were demonstrated in bronchoalveolar lavage. TIMP-1 and TIMP-2 were constitutively expressed, and only TIMP-1 displayed a moderate increase with hyperoxia. To elucidate transcriptional mechanisms for increased gelatinase B expression after hyperoxia, nuclear transcription factor-kappabeta activation was explored. Oxidative stress significantly increased the lung expression of nuclear transcription factor-kappabeta (p65) protein, and nuclear transcription factor-kappabeta activation and increased levels of gelatinases A and B were found in isolated type II alveolar cells obtained from hyperoxic rats. Conceivably, subacute hyperoxia induces excessive gelatinase activity, which may contribute to lung damage.

publication date

  • September 1998

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1853013

PubMed ID

  • 9736032

Additional Document Info

start page

  • 833

end page

  • 44

volume

  • 153

number

  • 3