title: The receptor for advanced glycation end-products supports lung tissue biomechanics.
abstract: The receptor for advanced glycation end-products (RAGE) and its soluble forms are predominantly expressed in lung but its physiological importance in this organ is not yet fully understood. Since RAGE acts as a cell adhesion molecule, we postulated its physiological importance in the respiratory mechanics. Respiratory function in a buffer-perfused isolated lung system and biochemical parameters of the lung were studied in young, adult, and old RAGE knockout (RAGE-KO) mice and wild-type (WT) mice. Lungs from RAGE-KO mice showed a significant increase in the dynamic lung compliance and a decrease in the maximal expiratory air flow independent of age-related changes. We also determined lower mRNA and protein levels of elastin in lung tissue of RAGE-KO mice. RAGE deficiency did not influence the collagen protein level, lung capillary permeability, and inflammatory parameters (TNF-α, high-mobility group box protein 1) in lung. Overexpressing RAGE as well as soluble RAGE in lung fibroblasts or cocultured lung epithelial cells increased the mRNA expression of elastin. Moreover, immunoprecipitation studies indicated a trans interaction of RAGE in lung epithelial cells. Our findings suggest the physiological importance of RAGE and its soluble forms in supporting the respiratory mechanics in which RAGE trans interactions and the influence on elastin expression might play an important role.
authors.affiliation: Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Halle (Saale Ernst-Grube-Str. 40, D-06120 Halle (Saale Germany. babett.bartling@uk-halle.de.
authors.forename: Samiya
authors.initials: S
authors.lastname: Al-Robaiy
authors.forename: Bettina
authors.initials: B
authors.lastname: Weber
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.forename: Claudius
authors.initials: C
authors.lastname: Diez
authors.forename: Paulina
authors.initials: P
authors.lastname: Rolewska
authors.forename: Rolf-Edgar
authors.initials: RE
authors.lastname: Silber
authors.forename: Babett
authors.initials: B
authors.lastname: Bartling
mesh_terms: D000375:Aging; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D008168:Lung / Q000502:physiology*; D008448:Maximal Expiratory Flow Rate / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C578573:Hmbox1 protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D004549:Elastin
keywords: aging; biomechanics; elastin; mouse; receptor for advanced glycation end-products