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:10469433
- 负责人:
- 金额:$ 63.64万
- 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.
宫内生长限制(IUGR)与围产节损伤有关
后来的心血管,肾脏和代谢疾病。因此,阐明了早期引起的机制
为了减少婴儿和成人,必须进行生长限制性新生儿的渐进器官危险
发病率和死亡率。 UROTENSIN II(UII),有效的血管活性肽调节肾功能,其水平为
患有心脏和肾脏疾病的婴儿增加。尽管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,即UII活动的增加导致肾功能不全
在增长的新生儿中。 UII通过Ca2+依赖性酪氨酸刺激外围交感神经兴奋
羟化酶磷酸化,儿茶酚胺生物合成和神经传递。引起同情的流出
由UII触发了新生儿的肾脏损伤。这些概念将在新生猪和临床前进行研究
自然不对称IUGR的猪模型。使用创新程序进行翻译
研究,我们将研究小胎龄新生猪中的肾功能,并阐明该功能和
UII系统的调节及其组件对1)变化的新生儿肾脏的贡献
血液动力学和2)肾脏限制婴儿的肾脏不足。我们预计我们的拟议研究将
对了解未成熟肾脏的病理生理学有重大影响。
项目成果
期刊论文数量(0)
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科研奖励数量(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
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 - 财政年份:2020
- 资助金额:
$ 63.64万 - 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:
10591881 - 财政年份:2020
- 资助金额:
$ 63.64万 - 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:
$ 63.64万 - 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:
$ 63.64万 - 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:
$ 63.64万 - 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:
$ 63.64万 - 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:
$ 63.64万 - 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:
$ 63.64万 - 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:
$ 63.64万 - 项目类别:
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尾加压素 II 和生长受限婴儿的肾功能不全。
- 批准号:
10264070 - 财政年份:2020
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$ 63.64万 - 项目类别:
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