Mechanisms of Renal Lipid Accumulation in Diabetic Nephropathy
糖尿病肾病肾脂质蓄积机制
基本信息
- 批准号:8391566
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-10-01 至 2013-09-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityAlbuminuriaAnimal ModelAntibodiesBindingBiological ModelsCellsCharacteristicsClinical ResearchComplicationComplications of Diabetes MellitusDataDepositionDevelopmentDiabetes MellitusDiabetic NephropathyEnalaprilEnd stage renal failureGoalsGrantHealthcareHigh PrevalenceHyperlipidemiaIn VitroIndividualInflammatoryKidneyKidney DiseasesLesionLeucineLinkLipidsLipoproteinsLow Density Lipoprotein ReceptorLow-Density LipoproteinsMediatingMediator of activation proteinModelingMorbidity - disease rateMusProteoglycanReportingResearchRoleTestingTherapeutic InterventionTissuesTransforming Growth Factor betaTranslatingUp-RegulationVeteransbiglycandiabeticglomerulosclerosisin vivoinhibitor/antagonistinterestmortalitymouse modelnephrogenesisneutralizing antibodynovelpreventpublic health relevancereceptor bindingresearch studytype I and type II diabetes
项目摘要
DESCRIPTION (provided by applicant):
Nephropathy is a major complication of both type 1 and type 2 diabetes which causes considerable morbidity and mortality. Despite best current treatments, significant numbers of individuals with albuminuria progress to end stage renal disease. Although the mechanisms underlying this progression are not fully understood, renal lipid and lipoprotein accumulation has been shown to accelerate the development of nephropathy. Renal lipid accumulation triggers an influx of inflammatory cells with subsequent development of glomerulosclerosis, the characteristic lesion of diabetic nephropathy. Glomerulosclerosis is characterized by increased deposition of mesangial matrix, including proteoglycans. Of particular interest, the renal content of the small leucine-rich proteoglycan (SLRP) biglycan is increased in diabetes. TGF-2, which is elevated in diabetes, and is known to be a key mediator of diabetic nephropathy development and progression, also increases mesangial matrix deposition, including increased expression of biglycan. Furthermore, we have shown that TGF-2 increases the size and LDL binding affinity of renal proteoglycans. Thus, increased renal proteoglycan (biglycan) synthesis induced by elevated TGF-2 in diabetes may be responsible for mediating the renal accumulation of lipoproteins. The overall goal of this grant is to test the hypothesis that renal lipid accumulation is mediated through interactions of lipoproteins with renal proteoglycans, especially biglycan. This will be tested by comparing diabetic nephropathy in mice expressing proteoglycan-binding defective LDL with littermates expressing wildtype LDL. To determine if biglycan is the key proteoglycan responsible, diabetic nephropathy will be compared between biglycan deficient and wildtype mice. The experiments outlined in this grant will provide direct in vivo experimental data identifying if proteoglycan mediated renal lipid accumulation contributes significantly to the development and progression of diabetic nephropathy, and if the key proteoglycan is biglycan. This grant will also identify if biglycan serves as a natural inhibitor of TGF-2 in vivo. Thus, the significance of this proposal is that it not only identifies a mechanism linking hyperlipidemia and diabetic nephropathy, but also will identify novel targets to prevent or intervene in the development of diabetic nephropathy.
描述(由申请人提供):
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Elevated circulating TGF-β is not the cause of increased atherosclerosis development in biglycan deficient mice.
循环 TGF-β 升高并不是双糖链蛋白聚糖缺陷小鼠动脉粥样硬化发展增加的原因。
- DOI:10.1016/j.atherosclerosis.2017.11.005
- 发表时间:2018
- 期刊:
- 影响因子:5.3
- 作者:Thompson,JoelC;Wilson,PatriciaG;Wyllie,AlexP;Wyllie,AdrianK;Tannock,LisaR
- 通讯作者:Tannock,LisaR
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LISA R TANNOCK其他文献
LISA R TANNOCK的其他文献
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{{ truncateString('LISA R TANNOCK', 18)}}的其他基金
Mechanisms linking obesity and abdominal aortic aneurysm
肥胖与腹主动脉瘤的联系机制
- 批准号:
10266037 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Mechanisms linking obesity and abdominal aortic aneurysm
肥胖与腹主动脉瘤的联系机制
- 批准号:
9974276 - 财政年份:2019
- 资助金额:
-- - 项目类别:
The association of SAA with apoB lipoproteins affects cardiovascular risk
SAA 与 apoB 脂蛋白的关联影响心血管风险
- 批准号:
8735744 - 财政年份:2014
- 资助金额:
-- - 项目类别:
The association of SAA with apoB lipoproteins affects cardiovascular risk
SAA 与 apoB 脂蛋白的关联影响心血管风险
- 批准号:
8822730 - 财政年份:2014
- 资助金额:
-- - 项目类别:
The association of SAA with apoB lipoproteins affects cardiovascular risk
SAA 与 apoB 脂蛋白的关联影响心血管风险
- 批准号:
8967203 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Mechanisms of Renal Lipid Accumulation in Diabetic Nephropathy
糖尿病肾病肾脂质蓄积机制
- 批准号:
7797702 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Mechanisms of Renal Lipid Accumulation in Diabetic Nephropathy
糖尿病肾病肾脂质蓄积机制
- 批准号:
8195615 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Angiotensin Induced Proteoglycans in Atherosclerosis
动脉粥样硬化中血管紧张素诱导的蛋白多糖
- 批准号:
7879773 - 财政年份:2009
- 资助金额:
-- - 项目类别:
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