A Critical Regulatory Role for Macrophage Migration Inhibitory Factor in Hyperoxia-Induced Injury in the Developing Murine Lung |
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Authors: | Huanxing Sun Rayman Choo-Wing Angara Sureshbabu Juan Fan Lin Leng Shuang Yu Dianhua Jiang Paul Noble Robert J. Homer Richard Bucala Vineet Bhandari |
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Affiliation: | 1. Department of Pediatrics, Yale University, New Haven, Connecticut, United States of America.; 2. Department of Medicine, Yale University, New Haven, Connecticut, United States of America.; 3. Department of Medicine, Duke University School of Medicine, Durham, North Carolina, United States of America.; 4. Department of Pathology, Yale University, New Haven, Connecticut, United States of America.; University of Washington, United States of America, |
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Abstract: | BackgroundThe role and mechanism of action of MIF in hyperoxia-induced acute lung injury (HALI) in the newborn lung are not known. We hypothesized that MIF is a critical regulatory molecule in HALI in the developing lung.MethodologyWe studied newborn wild type (WT), MIF knockout (MIFKO), and MIF lung transgenic (MIFTG) mice in room air and hyperoxia exposure for 7 postnatal (PN) days. Lung morphometry was performed and mRNA and protein expression of vascular mediators were analyzed.ResultsMIF mRNA and protein expression were significantly increased in WT lungs at PN7 of hyperoxia exposure. The pattern of expression of Angiopoietin 2 protein (in MIFKO>WT>MIFTG) was similar to the mortality pattern (MIFKO>WT>MIFTG) in hyperoxia at PN7. In room air, MIFKO and MIFTG had modest but significant increases in chord length, compared to WT. This was associated with decreased expression of Angiopoietin 1 and Tie 2 proteins in the MIFKO and MIFTG, as compared to the WT control lungs in room air. However, on hyperoxia exposure, while the chord length was increased from their respective room air controls, there were no differences between the 3 genotypes.ConclusionThese data point to the potential roles of Angiopoietins 1, 2 and their receptor Tie2 in the MIF-regulated response in room air and upon hyperoxia exposure in the neonatal lung. |
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