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:
- 金额:$ 55.59万
- 依托单位:
- 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:
- 关键词:Acute Renal Failure with Renal Papillary NecrosisAdultAnabolismAnimalsAttenuatedBirthBirth WeightCardiovascular DiseasesCardiovascular systemCatecholaminesCellsChronic Kidney FailureDataDenervationElderlyEnd stage renal failureExhibitsExocytosisFamily suidaeFetal Growth RetardationFunctional disorderGenerationsGlomerulonephritisGrowthHeart DiseasesHomeostasisHumanHypertensionImpaired Renal FunctionInfantInjury to KidneyIschemiaKidneyKidney DiseasesKidney FailureLeadLifeLinkLow Birth Weight InfantMetabolic DiseasesMicrocirculationModelingMolecularMorbidity - disease rateNADPH OxidaseNeonatalNeonatal Intensive CareNephrotic SyndromeNerveNeuronsNewborn InfantNorepinephrineOrganOxidative StressPeptidesPerfusionPerinatalPeripheralPharmacologyPhosphorylationPhysiologicalPlasmaPlayPre-Clinical ModelPremature BirthProceduresProductionReactive Oxygen SpeciesRegulationRenal functionReperfusion TherapyRiskRoleSepsisSignal TransductionSmall for Gestational Age InfantSystemTestingTranslational ResearchTyrosine 3-MonooxygenaseVenousearly onsetfetalhemodynamicshigh riskhypoperfusioninnovationmortalityneonateneurotransmissionnew therapeutic targetnovelorgan injuryporcine modelpre-clinicalpressurereceptorrenal ischemiatoolurotensin IIvasoconstriction
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.
胎儿宫内生长受限(IUGR)与围产期器官损伤和发生胎儿宫内发育不良的风险有关。
心血管、肾脏和代谢疾病。因此,阐明导致早期
生长受限的新生儿进行性器官紊乱是必要的,
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,其水平在
心脏和肾脏疾病的婴儿增加。尽管其生理和病理生理机制
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,我们提出了一个新的概念,即UII活性的增加有助于肾功能不全
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。交感神经流出
引起新生儿肾损伤。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。使用创新的翻译程序
研究,我们将研究小胎龄新生猪的肾功能,并阐明其功能和
UII系统的调节及其组分对1)新生儿肾脏
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有重要影响。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Adebowale Adebiyi其他文献
Adebowale Adebiyi的其他文献
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{{ truncateString('Adebowale Adebiyi', 18)}}的其他基金
Control of microvascular function by ion channels
离子通道控制微血管功能
- 批准号:
10591881 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
Control of microvascular function by ion channels
离子通道控制微血管功能
- 批准号:
10594479 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
Vascular ion channels and microcirculation in neonatal urinary tract obstruction
新生儿尿路梗阻的血管离子通道与微循环
- 批准号:
10341119 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
Control of microvascular function by ion channels
离子通道控制微血管功能
- 批准号:
10392350 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
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:
10469433 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
Vascular ion channels and microcirculation in neonatal urinary tract obstruction
新生儿尿路梗阻的血管离子通道与微循环
- 批准号:
9884233 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
Vascular ion channels and microcirculation in neonatal urinary tract obstruction
新生儿尿路梗阻的血管离子通道与微循环
- 批准号:
10565955 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
Control of microvascular function by ion channels
离子通道控制微血管功能
- 批准号:
10201230 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
Control of microvascular function by ion channels
离子通道控制微血管功能
- 批准号:
10808238 - 财政年份:2020
- 资助金额:
$ 55.59万 - 项目类别:
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