BackgroundReceptors for advanced glycation end-products (RAGE) are cell surface receptors prominently expressed by lung epithelium. Previous research demonstrated that over-expression of RAGE by murine alveolar epithelial cells during embryogenesis caused severe lung hypoplasia and neonatal lethality. However, the effects of RAGE over-expression on adjacent matrix and endothelial cells remained unknown.MethodsRAGE transgenic (TG) mice were generated that conditionally over-expressed RAGE in alveolar type II cells when fed doxycycline (dox) from conception to E18.5. To evaluate effects on the basement membrane, immunostaining and immunoblotting were performed for collagen IV and MMP-9, a matrix metalloprotease capable of degrading basement membranes. To assess changes in vasculature, immunostaining, immunoblotting and qRT-PCR were performed for Pecam-1, a platelet endothelial cell adhesion marker also known as CD31. Lastly, to characterize potential regulatory mechanisms of endothelial cell differentiation, immunoblotting and qRT-PCR for FoxM1, a key endothelium-specific transcription factor of the Forkhead Box (Fox) family, were completed.ResultsQualitative immunostaining for collagen IV was less in RAGE TG mice compared to controls and immunoblotting revealed decreased collagen IV in the RAGE TG mouse lung. Additionally, elevated MMP-9 detected via immunostaining and immunoblotting implicated MMP-9 as a possible down stream effector in matrix destabilization mediated by RAGE signaling. Lastly, Pecam-1 assessment revealed a decrease in the prevalence of microvascular endothelial cells coincident with FoxM1 abrogation in RAGE TG mice compared to controls.ConclusionsRAGE over-expression by alveolar epithelium weakened the basement membrane and associated matrix via increased MMP-9 activity. Furthermore, over-expression of RAGE inhibited FoxM1, suggesting that anomalous transcriptional control contributes to decreased endothelial cell prevalence in the TG mouse lung.
This paper, an output of an art research project, explores the agency of the aircraft landing gear compartment in global transfer. Through the prism of historical events involving aircraft preparing to land at London Heathrow, it reflects on the part played by the compartment in ecological and humanitarian struggle. Its theoretical frameworks include John Ruskin’s writing on geology, new materialism, and the planetary garden. These are brought into proximity with methodologies and collaborations developed through practice-based elements of the research, such as architectural modelling, geoforensic science and exhibition making. It incorporates an account of the process of reconstructing a compartment, as well as extracts from a microstratigraphic survey commissioned as part of the project. It examines the landing gear compartment’s capacity as a vessel in which dust, seeds, insects, pollen and even people are transported around the globe. It explores, too, its role as expository instrument, as far as it makes available for inspection the politics inscribed into its formal, spatial and temporal configuration. The paper argues that the wheel bay gives shape to a set of otherwise intangible aeromobilities, knowledge of which is integral to a nuanced understanding of the political geography of London Heathrow.
This paper, an output of an art research project, explores the agency of the aircraft landing gear compartment in global transfer. Through the prism of historical events involving aircraft preparing to land at London Heathrow, it reflects on the part played by the compartment in ecological and humanitarian struggle. Its theoretical frameworks include John Ruskin’s writing on geology, new materialism, and the planetary garden. These are brought into proximity with methodologies and collaborations developed through practice-based elements of the research, such as architectural modelling, geoforensic science and exhibition making. It incorporates an account of the process of reconstructing a compartment, as well as extracts from a microstratigraphic survey commissioned as part of the project. It examines the landing gear compartment’s capacity as a vessel in which dust, seeds, insects, pollen and even people are transported around the globe. It explores, too, its role as expository instrument, as far as it makes available for inspection the politics inscribed into its formal, spatial and temporal configuration. The paper argues that the wheel bay gives shape to a set of otherwise intangible aeromobilities, knowledge of which is integral to a nuanced understanding of the political geography of London Heathrow.
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