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

Annie Pardo*, Roberto Barrios, Vilma Maldonado, Jorge Meléndez, Julia Pérez, Víctor Ruiz, Lourdes Segura-Valdez, J. Iasha Sznajder, Moisés Selman

*Corresponding author for this work

Research output: Contribution to journalArticle

103 Scopus citations

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-κβ activation was explored. Oxidative stress significantly increased the lung expression of nuclear transcription factor- κβ (p65) protein, and nuclear transcription factor-κβ 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.

Original languageEnglish (US)
Pages (from-to)833-844
Number of pages12
JournalAmerican Journal of Pathology
Volume153
Issue number3
DOIs
StatePublished - Sep 1998

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Pardo, A., Barrios, R., Maldonado, V., Meléndez, J., Pérez, J., Ruiz, V., Segura-Valdez, L., Iasha Sznajder, J., & Selman, M. (1998). Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia: Pathogenetic implications. American Journal of Pathology, 153(3), 833-844. https://doi.org/10.1016/S0002-9440(10)65625-8