TY - JOUR
T1 - Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia
T2 - Pathogenetic implications
AU - Pardo, Annie
AU - Barrios, Roberto
AU - Maldonado, Vilma
AU - Meléndez, Jorge
AU - Pérez, Julia
AU - Ruiz, Víctor
AU - Segura-Valdez, Lourdes
AU - Iasha Sznajder, J.
AU - Selman, Moisés
PY - 1998/9
Y1 - 1998/9
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)65625-8
DO - 10.1016/S0002-9440(10)65625-8
M3 - Article
C2 - 9736032
AN - SCOPUS:0031659907
SN - 0002-9440
VL - 153
SP - 833
EP - 844
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -