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Urotensin II and renal insufficiency in growth-restricted infants.

尾加压素 II 和生长受限婴儿的肾功能不全。

基本信息

批准号：
10264070
负责人：
Adebowale Adebiyi
金额：
$ 55.59万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10264070
关键词：
Acute Renal Failure with Renal Papillary Necrosis Adult Anabolism Animals Attenuated Birth Birth Weight Cardiovascular Diseases Cardiovascular system Catecholamines Cells Chronic Kidney Failure Data Denervation Elderly End stage renal failure Exhibits Exocytosis Family suidae Fetal Growth Retardation Functional disorder Generations Glomerulonephritis Growth Heart Diseases Homeostasis Human Hypertension Impaired Renal Function Infant Injury to Kidney Ischemia Kidney Kidney Diseases Kidney Failure Lead Life Link Low Birth Weight Infant Metabolic Diseases Microcirculation Modeling Molecular Morbidity - disease rate NADPH Oxidase Neonatal Neonatal Intensive Care Nephrotic Syndrome Nerve Neurons Newborn Infant Norepinephrine Organ Oxidative Stress Peptides Perfusion Perinatal Peripheral Pharmacology Phosphorylation Physiological Plasma Play Pre-Clinical Model Premature Birth Procedures Production Reactive Oxygen Species Regulation Renal function Reperfusion Therapy Risk Role Sepsis Signal Transduction Small for Gestational Age Infant System Testing Translational Research Tyrosine 3-Monooxygenase Venous early onset fetal hemodynamics high risk hypoperfusion innovation mortality neonate neurotransmission new therapeutic target novel organ injury porcine model pre-clinical pressure receptor renal ischemia tool urotensin II vasoconstriction

项目摘要

Intrauterine growth restriction (IUGR) is associated with perinatal organ injury and the risk of developing cardiovascular, renal, and metabolic disorders in later life. Hence, elucidation of the mechanisms that cause early and progressive organ derangement in growth-restricted newborns is necessary to reduce infant and adult morbidity and mortality. Urotensin II (UII), a potent vasoactive peptide modulates renal function, and its levels are increased in infants with heart and kidney disease. Although its physiological and pathophysiological mechanisms are unresolved, recent evidence suggests that the UII system can promote neurotransmission, thereby altering organ function. Here, we propose a new concept that an increase in UII activity contributes to renal insufficiency in growth-restricted newborns. UII stimulates peripheral sympathoexcitation via Ca2+-dependent tyrosine hydroxylase phosphorylation, catecholamine biosynthesis, and neurotransmission. Sympathetic outflow elicited by UII triggers kidney injury in the neonates. These concepts will be investigated in newborn pigs and a preclinical porcine model of naturally-occurring human asymmetric IUGR. Using innovative procedures for translational research, we will study renal function in small-for-gestational-age neonatal pigs and elucidate the function and regulation of the UII system and the contribution of its components to 1) alterations in neonatal renal hemodynamics and 2) renal insufficiency in growth-restricted infants. We anticipate that our proposed studies will have a significant impact on understanding the pathophysiology of the immature kidney.

宫内生长限制（IUGR）与围产期器官损伤和发展的风险有关