A5053837630- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- Congenital Diaphragmatic Hernia Studies
- Growth Hormone and Insulin-like Growth Factors
- Digestive system and related health
- Diet and metabolism studies
- Stress Responses and Cortisol
- Genetics and Neurodevelopmental Disorders
- Anesthesia and Neurotoxicity Research
- Adipose Tissue and Metabolism
- Renal and related cancers
- Hormonal Regulation and Hypertension
- Gestational Diabetes Research and Management
- Infant Nutrition and Health
- Estrogen and related hormone effects
- Folate and B Vitamins Research
- GDF15 and Related Biomarkers
- Neonatal and fetal brain pathology
- Respiratory Support and Mechanisms
- RNA modifications and cancer
- Trace Elements in Health
- Neuroscience of respiration and sleep
- Genetic Syndromes and Imprinting
University of Utah
2008-2018
Howard Hughes Medical Institute
1999
United States Department of Veterans Affairs
1999
Vanderbilt University
1999
University of California, San Diego
1991
Abstract —The renin-angiotensin system is a major regulator of body sodium, predominantly through the actions intrarenal angiotensin II unclear origin. We show that polarized epithelium proximal tubule synthesizes and secretes angiotensinogen at its apical side protein can be detected in urine as function dietary sodium. Furthermore, we demonstrate renin expressed secreted restricted nephron segment, connecting tubule, also sodium-dependent fashion. A paracrine operating along entire may...
Intrauterine growth restriction (IUGR) decreases serum insulin factor-1 (IGF-1) levels. IGF-1 is an epigenetically regulated gene that has two promoters, alternative exon 5 splicing, and multiple termination sites. The regulation of expression involves the whole gene, as evidenced by aforementioned paradigm. We hypothesized IUGR in rat would affect hepatic alter epigenetic characteristics along its length. was induced through a bilateral uterine artery ligation pregnant rat,...
Maternal food restriction (FR) during pregnancy results in intrauterine growth-restricted (IUGR) offspring that show rapid catch-up growth and develop metabolic syndrome adult obesity. However, continued nutrient nursing delays prevents development of Epigenetic regulation IGF1, which modulates is synthesized secreted by the liver, may play a role these morbidities. Control (AdLib) pregnant rats received ad libitum through gestation lactation, FR dams were exposed to 50% from days 10 21....
Intrauterine growth retardation (IUGR) increases the risk of neuroendocrine reprogramming. In rat, IUGR leads to persistent changes in cerebral mRNA levels. This suggests lasting alterations transcriptional regulation, which may result from chromatin structure. Candidate nutritional triggers for these include altered zinc and one-carbon metabolite We hypothesized that affects structure neonatal postnatal rat brains. Rats were rendered by bilateral uterine artery ligation; controls (Con)...
Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of adult onset insulin resistance dyslipidemia in humans rats. IUGR rats are further characterized by postnatal alterations hepatic PPAR-gamma coactivator (PGC-1) carnitine-palmitoyl-transferase I (CPTI) expression, as well overall hyperacetylation histone H3. However, it is unknown whether H3 site specific or relates to changes gene expression previously described We therefore hypothesized...
Intrauterine growth restriction (IUGR) increases the risk of serious adult morbidities such as hypertension. In an IUGR rat model hypertension, we reported a persistent decrease in kidney 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) mRNA and protein levels from birth through postnatal (P) day 21. This enzyme deficiency can lead to hypertension by limiting renal glucocorticoid deactivation. present study, hypothesized that affects 11beta-HSD2 epigenetic determinants chromatin...
Uteroplacental insufficiency leads to intrauterine growth retardation (IUGR) and adult onset insulin resistance in both humans rats. IUGR rat liver is characterized by persistent changes histone 3 lysine 9 14 acetylation, which may induce postnatal gene expression. We hypothesized that it would be possible identify hepatic genes whose epigenetic characteristics mRNA levels are altered due using chromatin immunoprecipitation (ChIP) coupled with random primed differential display polymerase...
Rationale: Bronchopulmonary dysplasia (BPD) is a frequent cause of morbidity in preterm infants that characterized by prolonged need for ventilatory support an intensive care environment. BPD histopathologically persistently thick, cellular distal airspace walls. In normally developing lungs, comparison, remodeling the immature parenchymal architecture thinning future alveolar walls, process predicated on cell loss through apoptosis.Objectives: We hypothesized minimizing lung injury, using...
Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number predisposes toward renal early in life increased risk of adult-onset hypertension. In this study, we hypothesized the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein nephrogenesis, constitutes mechanism through which UPI subsequent glucocorticoid overexposure can decrease number. We further downregulates key 11beta-hydroxysteroid...
Studies in humans and rats suggest that intrauterine growth retardation (IUGR) permanently resets the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis reprogramming may involve persistently altered expression of hippocampal glucocorticoid receptor (hpGR), an important regulator reactivity. Persistent alteration gene expression, long after inciting event, is thought to be mediated by epigenetic mechanisms affect mRNA variant expression. GR variants both include eleven 5'-end GRalpha,...
Complications of intrauterine growth restriction (IUGR) include increased pulmonary morbidities and impaired alveolar development. Normal development depends upon elastin expression processing, as well the formation deposition elastic fibers. This is true human rat. In this study, we hypothesized that uteroplacental insufficiency (UPI)-induced IUGR decreases mRNA levels genes required for fiber synthesis assembly, at birth (prealveolarization) postnatal day 7 (midalveolarization) in We...
Abstract Intrauterine growth restriction (IUGR) increases the risk of postnatal lung disease, with males more affected. In rat lungs, IUGR impairs alveolarization in conjunction altered expression peroxisome proliferator‐activated receptor gamma (PPARγ). non‐lung cells, PPARγ transcription is regulated part by epigenetic modifying enzyme, and methyl CpG binding protein 2 (MeCP2). However, it unknown if affects MeCP2 or its interaction during alveolarization. this study, we hypothesized that...
Uteroplacental insufficiency (UPI), the major cause of intrauterine growth restriction (IUGR) in developed nations, predisposes to learning impairment. The underlying mechanism is unknown. Neuronal N-methyl-d-aspartate receptors (NMDARs) are critical for synaptogenesis and throughout life. We hypothesized that UPI-induced IUGR alters rat hippocampal NMDAR NR2A/NR2B subunit ratio and/or NR1 mRNA isoform expression synaptic density at day 21 (P21). To test this hypothesis, was induced by...
In utero environmental adaptation may predispose to lifelong morbidity. Organisms fine-tune gene expression achieve by epigenetic alterations of histone markers accessibility. One example epigenetics is how uteroplacental insufficiency-induced intrauterine growth restriction (IUGR), which predisposes adult onset insulin resistance, decreases postnatal IGF-1 mRNA variants and the elongation mark 3 trimethylation lysine 36 (H3Me3K36). Limitations in study exist due lack a primary transgenic...
Intrauterine growth restriction (IUGR) decreases serum IGF-1 levels. Postnatal expression is transcriptionally regulated by hormone (GH) through response elements (GHREs). We hypothesized that IUGR disrupts the normal developmental maturation of hepatic intron 2 element (IN2GHRE) histone methylation key lysines and DNA methylation. also evaluated a 5' distal weak enhancer (IGF-15'-upstream region element; 5URGHRE) as GHRE specificity control. was induced well-characterized model bilateral...
Intrauterine growth restriction (IUGR) increases the incidence of chronic lung disease (CLD). The molecular mechanisms responsible for IUGR-induced acute injury that predispose IUGR infant to CLD are unknown. p53, a transcription factor, plays pivotal role in determining cellular response stress by affecting apoptosis, cell cycle regulation, and angiogenesis, processes required thinning mesenchyme. Because thickened mesenchyme is characteristic CLD, we hypothesized changes associated with...
Severe uteroplacental insufficiency causes cerebral apoptosis in the fetus. Moderate intrauterine growth retardation (IUGR) and increases risk of postnatal neurological morbidity. In rat, IUGR affect gene expression Bcl-2 predispose newborn rat toward when challenged with perinatal hypoxia. Expression Bcl-2, as well proapoptotic protein Bax, is regulated by p53. p53 also induces MDM2 transcription, which functions to limit further p53-induced apoptosis. The predisposition fetus suggests that...
Uteroplacental insufficiency (UPI) induces persistent changes in hepatic gene expression secondary to altered chromatin dynamics the intrauterine growth- restricted (IUGR) rat liver. The glucocorticoid receptor (GR) is a transcription factor that when activated can induce structure. To begin process of identifying pathways by which IUGR affects structure, we hypothesized UPI significant increase endogenous glucocorticoids (corticosterone) and increases GR activation. prove our hypothesis,...
Intrauterine growth retardation (IUGR) predisposes humans toward hippocampal morbidities, such as impaired learning and memory. Hippocampal dual specificity phosphatase 5 (DUSP5) may be involved in these morbidities because DUSP5 regulates extracellular signal-regulated kinase phosphorylation (Erk). In the rat, IUGR causes postnatal changes gene expression epigenetic characteristics. However, impact of upon characteristics is not known. We therefore hypothesized that affects 1) expression,...