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Full-Text Articles in Physiology
Rage And Sage: Therapeutic Modalities For Copd, Paul Reynolds
Rage And Sage: Therapeutic Modalities For Copd, Paul Reynolds
Journal of Undergraduate Research
Funding available through this MEG award has provided an opportunity for me to meet many academic objectives I’ve determined to be important at BYU. We have been successful in conducting pilot studies that reveal possible roles for SAGEs in ameliorating mechanisms of lung inflammation induced by and cigarette smoke (CS). Despite improvement in personal air quality during the past few decades, the rationale for studying mechanisms leading to adverse health effects remains important. This MEG award specifically provided opportunities for students to conduct meaningful research that led to the observation that alveolar epithelial cells and bronchiolar epithelial cells experience elevated …
Rage Functions During Secondhand Smoke-Induced Bronchopulmonary Dysplasia, Brent Kimber, Dr. Paul Reynolds
Rage Functions During Secondhand Smoke-Induced Bronchopulmonary Dysplasia, Brent Kimber, Dr. Paul Reynolds
Journal of Undergraduate Research
Bronchopulmonary Dysplasia (BPD) is a common respiratory disease among pre-term infants or newborns exposed to harmful toxins during pregnancy or at birth. This leads to several respiratory diseases later in life such as chronic obstructive pulmonary disorder (COPD) or asthma. However, research on the effects of cigarette smoke in utero has many gaps. This project focuses on developing a transgenic mouse model that mimics the pulmonary morphologies and characteristics of BPD. This model will then be used for further research and potentially discover new therapeutic methods for BPD. The transgenic mouse was established using a modified genetic scheme whereby the …
Differential Receptors For Advanced Glycation End-Products (Rage) Expression In Preeclampsia, Intrauterine Growth Restriction And Gestational Diabetes, Kristen Lena Alexander
Differential Receptors For Advanced Glycation End-Products (Rage) Expression In Preeclampsia, Intrauterine Growth Restriction And Gestational Diabetes, Kristen Lena Alexander
Theses and Dissertations
Preeclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes (GDM) increase the risk of maternal and fetal morbidity and mortality. The roles of Advanced Glycation End-products (AGEs) are already well documented concerning inflammation, hypoxia and oxidative stress. AGEs bind to its receptor, Receptor for Advanced Glycation End-products (RAGE), and activate an inflammatory pathway. This pathway alters the efficacy of invasive trophoblast cells and in the placenta and can result in placental dysfunction. We hypothesized that the placental dysfunction found in PE, IUGR, and GDM resulted from an over activation of the RAGE-mediated inflammatory pathway. Using human placental samples, we found …
Hmgb1 And Ceramides: Potential Mediators Of Cigarette Smoke-Induced Metabolic Dysfunction, Mikayla Orton Thatcher
Hmgb1 And Ceramides: Potential Mediators Of Cigarette Smoke-Induced Metabolic Dysfunction, Mikayla Orton Thatcher
Theses and Dissertations
While cigarette smoking is a common-knowledge way to stay lean, it has long been known as a risk factor for diabetes and obesity. Here we establish that smoking causes fat gain and metabolic disruption in mice, effects which are exacerbated by a high-fat, high-sugar diet. We found that smoke exposure increases levels of ceramide—the lipid responsible for diet-induced insulin resistance—and that blocking ceramide production with the pharmacological inhibitor myriocin restored insulin sensitivity, stopped weight gain, and rescued mitochondrial respiration in vivo and in vitro.We also sought to assess the impact of the RAGE ligand HMGB1 on skeletal muscle metabolism. We …
Effects Of Blocking Tlr 4 And Rage On The Progression Of Oa In The Tmj, David Mecham, David Kooyman
Effects Of Blocking Tlr 4 And Rage On The Progression Of Oa In The Tmj, David Mecham, David Kooyman
Journal of Undergraduate Research
Osteoarthritis is a degenerative disease of the cartilage that affects more than 80% of Americans above the age of 65 (1). Many adults also suffer from Temporomandibular joint dysfunction (TMD), and 80% of such individuals eventually develop Temporomandibular joint associated Osteoarthritis (TMJ OA) (2). Current pharmaceutical options target symptoms of OA, but there are no known treatments available. Research is being undertaken to elucidate the root causes of the disease at a cellular level. Our lab has previously shown that mice lacking the Receptor for Advanced Glycation End Products are protected from OA (3). Other researchers have shown that blocking …
The Role Of Receptors For Advanced Glycation End-Products (Rage) And Ceramide In Cardiovascular Disease, Michael Bruce Nelson
The Role Of Receptors For Advanced Glycation End-Products (Rage) And Ceramide In Cardiovascular Disease, Michael Bruce Nelson
Theses and Dissertations
Type 2 diabetes and cigarette smoke exposure are associated with an increased risk of cardiovascular complications. The role of advanced glycation end-products (AGEs) is already well-established in numerous comorbidities including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with carboxy-methyl lysine-BSA, followed by mitochondrial respiration assessment. We found that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when co-treated with myriocin, an inhibitor of de novo …
Targeting Of Receptors For Advanced Glycation End-Products (Rage) Diminishes Acute Secondhand Smoke-Induced Inflammation In Mice, Tyler Thomas Wood
Targeting Of Receptors For Advanced Glycation End-Products (Rage) Diminishes Acute Secondhand Smoke-Induced Inflammation In Mice, Tyler Thomas Wood
Theses and Dissertations
The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in pro-inflammatory signaling and its role in irreversible pulmonary remodeling. The current research evaluated for the first time the in vivo effects of short-term tobacco smoke exposure in RAGE null and control mice compared to identical animals exposed to room air only. Quantitative real time PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after four weeks of exposure and an anticipated …
Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias
Expression Of Osteoarthritis Biomarkers In Temporomandibular Joints Of Mice With And Without Receptor For Advanced Glycation End Products (Rage), Elizabeth Murayama Chavez Matias
Theses and Dissertations
This thesis will be organized into three chapters discussing the mechanism underlying the onset and progression of osteoarthritis (OA) in the temporomandibular joint (TMJ). Understanding the mechanism of OA development in the TMJ helps in understanding how OA progresses and how to treat this disease. The goal of this investigation is to examine the process of cartilage degeneration and OA biomarker expression in the TMJ to understand their role in TMJ OA onset and development.Chapter one covers mechanisms that are altered in TMJ OA during disease progression. Using animal models with different stressors such as mechanical disturbances, direct injury, and …
Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden
Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden
Theses and Dissertations
Receptors for advanced glycation end-products (RAGE) are pattern recognition receptors of the immunoglobulin superfamily highly expressed in the lung. Likely functions include the modulation of pulmonary inflammation during disease. However, the contributions of RAGE in the developing lung in cases where secondhand smoke (SHS) exposure occurs are unknown. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, we exposed gestating dams to a controlled dose of SHS during the last four critical days of in utero lung morphogenesis. We discovered that both maternal and fetal lungs respond to SHS by up-regulating RAGE. Exposed fetuses were markedly …
The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson
The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson
Theses and Dissertations
Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors of the immunoglobin family expressed by epithelium and macrophages. RAGE expression increases following ligand binding and when diverse cells are exposed to a variety of insults including cigarette smoke extract (CSE). The current research sought to characterize the pro-inflammatory contributions of RAGE expressed by alveolar macrophages (AMs) following CSE exposure. Acute exposure of mice to CSE via nasal instillation revealed diminished bronchoalveolar lavage (BAL) cellularity and fewer AMs in RAGE null mice compared to controls. Primary AMs were obtained from BAL, exposed to CSE in vitro, and RNA, DNA, …
Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill
Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill
Theses and Dissertations
Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors highly expressed in the lung that modulate pulmonary inflammation during disease. However, the contributions of RAGE signaling are unknown during pulmonary organogenesis. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that over-express RAGE in alveolar type II cells of the lung. When RAGE is over-expressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. Flow cytometry and immunohistochemistry employing cell-specific markers for various distal cell types demonstrated anomalies in key epithelial cell populations resulting from RAGE up-regulation through …