Characterization of Secondhand Smoke (SHS) and Materno-Fetal Interactions in Receptors for Advanced Glycation End-Products (RAGE)-Targeted Mice

摘要: Characterization of Secondhand Smoke (SHS) and Materno-Fetal Interactions in Receptors for Advanced Glycation End-Products (RAGE)-Targeted Mice Duane Ray Winden Department Physiology Developmental Biology, BYU Doctor Philosophy advanced glycation end-products (RAGE) are pattern recognition receptors the immunoglobulin superfamily highly expressed lung. Likely functions include modulation pulmonary inflammation during disease. However, contributions RAGE developing lung cases where secondhand smoke exposure occurs unknown. In order to test hypothesis that misexpression adversely affects morphogenesis, we exposed gestating dams a controlled dose SHS last four critical days utero morphogenesis. We discovered both maternal fetal lungs respond by upregulating RAGE. Exposed fetuses were markedly smaller compared controls compromised terms apoptotic status, collagen abundance necessary derivation respiratory compartments, expression MMP-9, protease known target extracellular matrix. Interestingly, knock out animals similarly protected, part, from same SHS-mediated abnormalities. next generated conditional transgenic mouse provided an opportunity genetically augment distal absence exposure. Our mice (RAGE TG) severely hypoplastic ultrastructural analysis demonstrated weakened basement membranes TG controls. Specific observations included diminished type IV required membrane derivation, augmented MMP-9 expression, inhibition vasculature visualized Pecam-1 staining, marker vascular endothelial cells. The further observation FoxM1, transcriptional regulator cell differentiation, was inhibited suggested novel potential mechanism impaired vascularization mediated These data provide evidence must be tightly regulated organogenesis. Furthermore, additional research into nuances signaling development may shed needed light on pathobiochemistry adult diseases potentially have origins.