Background: The formation of discrete elastin bands at the tips of secondary alveolar septa is important for normal\nalveolar development, but the mechanisms regulating the lung elastogenic program are incompletely understood.\nJNK suppress elastin synthesis in the aorta and is important in a host of developmental processes. We sought to\ndetermine whether JNK suppresses pulmonary fibroblast elastogenesis during lung development.\nMethods: Alveolar size, elastin content, and mRNA of elastin-associated genes were quantitated in wild type and\nJNK-deficient mouse lungs, and expression profiles were validated in primary lung fibroblasts. Tropoelastin protein\nwas quantitated by Western blot. Changes in lung JNK activity throughout development were quantitated, and\npJNK was localized by confocal imaging and lineage tracing.\nResults: By morphometry, alveolar diameters were increased by 7% and lung elastin content increased 2-fold in\nJNK-deficient mouse lungs compared to wild type. By Western blot, tropoelastin protein was increased 5-fold in\nJNK-deficient lungs. Postnatal day 14 (PND14) lung JNK activity was 11-fold higher and pJNK:JNK ratio 6-fold higher\ncompared to PN 8 week lung. Lung tropoelastin, emilin-1, fibrillin-1, fibulin-5, and lysyl oxidase mRNAs inversely\ncorrelated with lung JNK activity during alveolar development. Phosphorylated JNK localized to pulmonary\nlipofibroblasts. PND14 JNK-deficient mouse lungs contained 7-fold more tropoelastin, 2,000-fold more emilin-1,\n800-fold more fibrillin-1, and 60-fold more fibulin-5 than PND14 wild type lungs. Primarily lung fibroblasts from\nwild type and JNK-deficient mice showed similar differences in elastogenic mRNAs.\nConclusions: JNK suppresses fibroblast elastogenesis during the alveolar stage of lung development
Loading....