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。

• 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
• 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

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.

宫内生长受限 (IUGR) 与围产期器官损伤和发生胎儿畸形的风险相关。 晚年的心血管、肾脏和代谢疾病。因此，阐明早期发生的机制 生长受限的新生儿进行性器官紊乱对于减少婴儿和成人的病情是必要的 发病率和死亡率。尾加压素 II (UII) 是一种有效的血管活性肽，可调节肾功能，其水平为 患有心脏病和肾脏疾病的婴儿的比例增加。虽然其生理和病理生理机制 尚未解决，最近的证据表明 UII 系统可以促进神经传递，从而改变 器官功能。在这里，我们提出了一个新概念：UII 活性增加会导致肾功能不全 生长受限的新生儿。 UII 通过 Ca2+ 依赖性酪氨酸刺激外周交感神经兴奋 羟化酶磷酸化、儿茶酚胺生物合成和神经传递。引起交感神经流出 UII 引起的新生儿肾损伤。这些概念将在新生猪和临床前研究中进行研究 自然发生的人类不对称IUGR的猪模型。使用创新程序进行转化 研究中，我们将研究小于胎龄新生猪的肾功能，并阐明其功能和 UII 系统的调节及其组成部分对 1) 新生儿肾功能改变的贡献 血流动力学和 2) 生长受限婴儿的肾功能不全。我们预计我们提出的研究将 对了解未成熟肾脏的病理生理学具有重要影响。