ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS
ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS
批准号:
3776700
负责人:
L J STRIKER
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
RNase protection assay albumins basement membrane collagen crosslink diabetic nephropathy extracellular matrix fibronectins genetic regulation glomerulosclerosis glucose metabolism glycosylation heparan sulfate hyperglycemia kidney cell laboratory mouse laboratory rat laminin macrophage messenger RNA nuclear runoff assay platelet derived growth factor proteoglycan receptor binding vascular endothelium
中文摘要
终末期肾小球硬化是糖尿病的主要并发症
糖尿病。 事实上,在胰岛素依赖型糖尿病和非胰岛素依赖型糖尿病肾小球病变,
类似的结果表明,葡萄糖代谢异常可能参与
in their其development发展. 高血压导致高级
糖基化终产物。 这些产品参与异常,非-
细胞外基质成分的可代谢交联。他们的
积累可能导致糖尿病患者中观察到的硬化。 年龄
引发大量的生物反应,
已经在巨噬细胞、内皮细胞、
细胞以及人和大鼠系膜细胞。使用正常小鼠系膜
细胞,我们研究了AGE对基底膜合成的影响。
膜组件接种在AGE上的细胞显示出增加的
使用RNA酶保护测定的下列mRNA:IV型胶原,
蛋白聚糖硫酸乙酰肝素和层粘连蛋白A和B链。 我们还发现
IV型胶原蛋白向培养基中的释放增加。率
转录,通过核径流测定法测量,也刺激了
将细胞铺在糖基化牛血清白蛋白上。AGE受体抗体
抑制了mRNA的增加。PDGF抗体消除了
年龄反应。由于这些观察是在体外进行的,我们检查了
对完整动物施用AGEs是否会产生类似的
方面的影响.正常小鼠的肾小球接受重复注射
AGEs表现出编码α 1 IV型胶原蛋白的mRNAS增加,
对于层粘连蛋白的B1链,确定存在肾小球
对AGEs的反应。
英文摘要
End-stage glomerulosclerosis constitutes a major complication of diabetes
mellitus. The fact that the glomerular lesions in both IDDM and NIDDM are
similar suggests that abnormalities in glucose metabolism may participate
in their development. Hyperglycemia leads to the accumulation of advanced
glycosylation end-products. These products participate in abnormal, non-
metabolizable cross-linking of extra-cellular matrix components. Their
accumulation may contribute to the sclerosis observed in diabetics. AGEs
trigger a large number of biological reactions which are mediated by
surface receptors that have been characterized on macrophages, endothelial
cells, and human and rat mesangial cells. Using normal mouse mesangial
cells, we investigated the effect of AGE on the synthesis of the basement
membrane components. Cells plated on AGE showed increased levels of the
following mRNAs using the RNAse protection assay: collagen type IV,
proteoglycan heparan sulfate, and laminin A and B chains. We also found
an increased release of collagen type IV into the medium. The rate of
transcription, measured by nuclear run-off assays, was also stimulated in
cells plated on glycosylated bovine serum albumin. AGE receptor antibodies
inhibited the observed increase in mRNAs. Antibodies to PDGF abrogated the
AGE response. Since these observations were made in vitro we have examined
whether the administration of AGEs to the intact animal would have similar
effects. The glomeruli of normal mice receiving repeated injections of
AGEs exhibited an increase in mRNAS coding for alpha1 type IV collagen and
for the Bl chain of laminin establishing that there is a glomerular
response to AGEs in vivo.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
PRODUCTION OF METALLOPROTEINASES AND TIMPS BY GLOMERULAR CELLS
-
批准号:5202003
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
GLOMERULAR LESIONS IN NON-OBESE DIABETIC MICE
-
批准号:3754539
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
PRODUCTION OF METALLOPROTEINASES AND TIMPS BY GLOMERULAR CELLS
-
批准号:6161985
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
DEGRADATION OF EXTRACELLULAR MATRIX IN HUMAN GLOMERULI
-
批准号:3754545
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
GLOMERULAR LESIONS IN MICE TRANSGENIC FOR GROWTH HORMONE
-
批准号:6161981
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
GENETICS OF GLOMERULAR DISEASE IN MICE
-
批准号:6161986
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
RENAL LESIONS IN THE ABLATION MODEL--ROLE OF GROWTH FACTORS
-
批准号:3855328
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
GLOMERULAR LESIONS IN NON-OBESE DIABETIC MICE
-
批准号:3855331
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
GLOMERULAR LESIONS IN NON-OBESE DIABETIC MICE
-
批准号:3840305
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
DEGRADATION OF EXTRACELLULAR MATRIX IN HUMAN GLOMERULI
-
批准号:5202007
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
STUDIES OF THE PATHOGENESIS OF GLOMERULOSCLEROSIS
-
批准号:5202006
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
DEGRADATION OF EXTRACELLULAR MATRIX IN HUMAN GLOMERULI
-
批准号:3840311
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
RENAL LESIONS IN NON-OBESE DIABETIC MICE
-
批准号:3876400
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
STUDIES OF THE PATHOGENESIS OF GLOMERULOSCLEROSIS
-
批准号:3754544
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
RENAL LESIONS IN THE ABLATION MODEL
-
批准号:3840303
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS
-
批准号:3840306
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
RENAL LESIONS IN THE ABLATION MODEL--ROLE OF GROWTH FACTORS
-
批准号:3876397
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
ADVANCED GLYCOSYLATION END PRODUCTS AND EFFECT OF MESANGIAL CELLS
-
批准号:3855332
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
RENAL LESIONS IN THE ABLATION MODEL
-
批准号:3754538
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
RENAL LESIONS IN THE ABLATION MODEL
-
批准号:3776697
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:L J STRIKER
-
依托单位:
海外基金